Skip to main content

Advertisement

SpringerLink
Log in

Immune cell engineering: opportunities in lung cancer therapeutics

  • Review Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Engineered immune cells offer a prime therapeutic alternate for some aggressive and frequently occurring malignancies like lung cancer. These therapies were reported to result in tumor regression and overall improvement in patient survival. However, studies also suggest that the presence of cancer cell-induced immune-suppressive microenvironment, off-target toxicity, and difficulty in concurrent imaging are some prime impendent in the success of these approaches. The present article reviews the need and significance of the currently available immune cell-based strategies for lung cancer therapeutics. It also showcases the utility of incorporating nanoengineered strategies and details the available formulations of nanocarriers. In last, it briefly discussed the existing methods for nanoparticle fuctionalization and challenges in translating basic research to the clinics.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. https://doi.org/10.3322/caac.21492.

    Article  PubMed  Google Scholar 

  2. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to the 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 2015;10:1240–2. https://doi.org/10.1097/JTO.0000000000000663.

    Article  PubMed  Google Scholar 

  3. Yatabe Y, Dacic S, Borczuk AC, et al. Best practices recommendations for diagnostic immunohistochemistry in lung cancer. J Thorac Oncol. 2019;14:377–407. https://doi.org/10.1016/j.jtho.2018.12.005.

    Article  CAS  PubMed  Google Scholar 

  4. Lemjabbar-Alaoui H, Hassan OU, Yang YW, Buchanan P. Lung cancer: biology and treatment options. Biochim Biophys Acta. 1856;2015:189–210. https://doi.org/10.1016/j.bbcan.2015.08.002.

    Article  CAS  Google Scholar 

  5. Arnold M, Rutherford MJ, Bardot A, et al. Progress in cancer survival, mortality, and incidence in seven high-income countries 1995-2014 (ICBP SURVMARK-2): a population-based study. Lancet Oncol. 2019;20:1493–505. https://doi.org/10.1016/S1470-2045(19)30456-5.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Liao Y, Wang X, Zhong P, Yin G, Fan X, Huang C. A nomogram for the prediction of overall survival in patients with stage II and III non-small cell lung cancer using a population-based study. Oncol Lett. 2019;18:5905–16. https://doi.org/10.3892/ol.2019.10977.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Santarpia M, Giovannetti E, Rolfo C, Karachaliou N, González-Cao M, Altavilla G, et al. Recent developments in the use of immunotherapy in non-small cell lung cancer. Expert Rev Respir Med. 2016;10:781–98. https://doi.org/10.1080/1747634820161182866.

    Article  CAS  PubMed  Google Scholar 

  8. Kibirova A, Mattes MD, Smolkin M, Ma PC. The journey of an EGFR-mutant lung adenocarcinoma through erlotinib, osimertinib and ABCP immunotherapy regimens: sensitivity and resistance. Case Rep Oncol. 2019;12:765–76. https://doi.org/10.1159/000503417.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Govindan R, Szczesna A, Ahn MJ, et al. Phase III trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol. 2017;35:3449–57. https://doi.org/10.1200/JCO.2016.71.7629.

    Article  CAS  PubMed  Google Scholar 

  10. Frederickson AM, Arndorfer S, Zhang I, et al. Pembrolizumab plus chemotherapy for first-line treatment of metastatic nonsquamous non-small-cell lung cancer: a network meta-analysis. Immunotherapy. 2019;11:407–28. https://doi.org/10.2217/imt-2018-0193.

    Article  CAS  PubMed  Google Scholar 

  11. Boloker G, Wang C, Zhang J. Updated statistics of lung and bronchus cancer in United States (2018). J Thorac Dis. 2018;10:1158–61. https://doi.org/10.21037/jtd20190296.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Griswold CR, Kerrigan K, Patel SB. Combination of local ablative therapy and continuation of immune checkpoint inhibitor (ICI) therapy provides durable treatment response past oligometastatic progression in NSCLC: a case report. Case Rep Oncol. 2019;12:866–71. https://doi.org/10.1159/000504473.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen Y, Zhou Y, Tang L, Peng X, Jiang H, Wang G, et al. Immune-checkpoint inhibitors as the first line treatment of advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials. J Cancer. 2019;10:6261–8. https://doi.org/10.7150/jca.34677.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Spaas M, Lievens Y. Is the combination of immunotherapy and radiotherapy in non-small cell lung cancer a feasible and effective approach? Front Med (Lausanne). 2019;6:244. https://doi.org/10.3389/fmed.2019.00244.

    Article  Google Scholar 

  15. Xu Y, Wan B, Chen X, Zhan P, Zhao Y, Zhang T, et al. The association of PD-L1 expression with the efficacy of anti-PD-1/PD-L1 immunotherapy and survival of non-small cell lung cancer patients: a meta-analysis of randomized controlled trials. Transl Lung Cancer Res. 2019;8:413–28. https://doi.org/10.21037/tlcr.2019.08.09.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ferro S, Huber V, Rivoltini L. Mechanisms of tumor immunotherapy, with a focus on thoracic cancers. J Thorac Dis. 2018;10:4619–31. https://doi.org/10.21037/jtd.2018.07.30.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Bhargava A, Mishra DK, Jain SK, Srivastava RK, Lohiya NK, Mishra PK. Comparative assessment of lipid based nano-carrier systems for dendritic cell based targeting of tumor re-initiating cells in gynecological cancers. Mol Immunol. 2016;79:98–112. https://doi.org/10.1016/jmolimm201610003.

    Article  CAS  PubMed  Google Scholar 

  18. Bhargava A, Mishra D, Banerjee S, Mishra PK. Dendritic cell engineering for tumor immunotherapy: from biology to clinical translation. Immunotherapy. 2012;4:703–18. https://doi.org/10.2217/imt1240.

    Article  CAS  PubMed  Google Scholar 

  19. Bhargava A, Mishra D, Khan S, Varshney SK, Banerjee S, Mishra PK. Assessment of tumor antigen-loaded solid lipid NPs as an efficient delivery system for dendritic cell engineering. Nanomedicine (London). 2013;8:1067–84. https://doi.org/10.2217/nnm12164.

    Article  CAS  Google Scholar 

  20. Duong CP, Yong CS, Kershaw MH, Slaney CY, Darcy PK. Cancer immunotherapy utilizing gene-modified T-cells: from the bench to the clinic. Mol Immunol. 2015;67:46–57. https://doi.org/10.1016/jmolimm2014.12009.

    Article  CAS  PubMed  Google Scholar 

  21. Met Ö, Jensen KM, Chamberlain CA, Donia M, Svane IM. Principles of adoptive T-cell therapy in cancer. Semin Immunopathol. 2019;41:49–58. https://doi.org/10.1007/s00281-018-0703-z.

    Article  PubMed  Google Scholar 

  22. Yee C. Adoptive T-cell therapy: points to consider. Curr Opin Immunol. 2018;51:197–203. https://doi.org/10.1016/jcoi201804007.

    Article  CAS  PubMed  Google Scholar 

  23. Sharpe M, Mount N. Genetically modified T-cells in cancer therapy: opportunities and challenges. Dis Model Mech. 2015;8:337–50. https://doi.org/10.1242/dmm018036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen D, Yang J. Development of novel antigen receptors for CAR T-cell therapy directed toward solid malignancies. Transl Res. 2017;187:11–21. https://doi.org/10.1016/jtrsl2017.05.006.

    Article  CAS  PubMed  Google Scholar 

  25. Wang X, Riviere I. Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies. Cancer Gene Ther. 2015;22:85–94. https://doi.org/10.1038/cgt.2014.81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Spear TT, Nagato K, Nishimura MI. Strategies to genetically engineer T-cells for cancer immunotherapy. Cancer Immunol Immunother. 2016;65:631–49. https://doi.org/10.1007/s00262-016-1842-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Zeltsman M, Dozier J, McGee E, Ngai D, Adusumilli PS. CAR T-cell therapy for lung cancer and malignant pleural mesothelioma. Transl Res. 2017;187:1–10. https://doi.org/10.1016/jtrsl.2017.04.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lichtman EI, Dotti G. Chimeric antigen receptor T-cells for B-cell malignancies. Transl Res. 2017;187:59–82. https://doi.org/10.1016/jtrsl.2017.06.011.

    Article  CAS  PubMed  Google Scholar 

  29. Townsend MH, Shrestha G, Robison RA, O'Neill KL. The expansion of targetable biomarkers for CAR T-cell therapy. J Exp Clin Cancer Res. 2018;37:163. https://doi.org/10.1186/s13046-018-0817-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Jung IY, Lee J. Unleashing the therapeutic potential of CAR-T-cell therapy using gene-editing technologies. Mol Cell. 2018;41:717–23. https://doi.org/10.14348/molcells20180242.

    Article  CAS  Google Scholar 

  31. Gacerez AT, Hua CK, Ackerman ME, Sentman CL. Chimeric antigen receptors with human scFvs preferentially induce T-cell anti-tumor activity against tumors with high B7H6 expression. Cancer Immunol Immunother. 2018;67:749–59. https://doi.org/10.1007/s00262-018-2124-1.

    Article  CAS  PubMed  Google Scholar 

  32. Rafiq S, Yeku OO, Jackson HJ, et al. Targeted delivery of a PD-1-blocking scFv by CAR-T-cells enhances anti-tumor efficacy in vivo. Nat Biotechnol. 2018;36:847–56. https://doi.org/10.1038/nbt.4195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bigley AB, Simpson RJ. NK-cells and exercise: implications for cancer immunotherapy and survivorship. Discov Med. 2015;19:433–45.

    PubMed  Google Scholar 

  34. Knorr DA, Bachanova V, Verneris MR, Miller JS. Clinical utility of natural killer cells in cancer therapy and transplantation. Semin Immunol. 2014;26:161–72. https://doi.org/10.1016/jsmim201402.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Dianat-Moghadam H, Rokni M, Marofi F, Panahi Y, Yousefi M. Natural killer cell-based immunotherapy: from transplantation toward targeting cancer stem cells. J Cell Physiol. 2018;234:259–73. https://doi.org/10.1002/jcp.26878.

    Article  CAS  PubMed  Google Scholar 

  36. Klingemann H, Boissel L, Toneguzzo F. Natural killer cells for immunotherapy - advantages of the NK-92 cell line over blood NK cells. Front Immunol. 2016;7:91. https://doi.org/10.3389/fimmu2016.00091.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Sakamoto N, Ishikawa T, Kokura S, et al. Phase I clinical trial of autologous NK cell therapy using novel expansion method in patients with advanced digestive cancer. J Transl Med. 2015;13:277. https://doi.org/10.1186/s12967-015-0632-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Delgado D, Webster DE, DeSantes KB, Durkin ET, Shaaban AF. KIR receptor-ligand incompatibility predicts killing of osteosarcoma cell lines by allogeneic NK cells. Pediatr Blood Cancer. 2010;55:1300–5. https://doi.org/10.1002/pbc.22665.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ichise H, Nagano S, Maeda T, et al. NK cell alloreactivity against KIR-ligand-mismatched HLA-haploidentical tissue derived from HLA haplotype-homozygous iPSCs. Stem Cell Reports. 2017;9:853–67. https://doi.org/10.1016/jstemcr.2017.07.020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Murakami T, Nakazawa T, Natsume A, et al. Novel human NK cell line carrying CAR targeting EGFRvIII induces antitumor effects in glioblastoma cells. Anticancer Res. 2018;38:5049–56. https://doi.org/10.21873/anticanres12824.

    Article  CAS  PubMed  Google Scholar 

  41. Tang X, Yang L, Li Z, et al. First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Am J Cancer Res. 2018;8:1083–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Bollino D, Webb TJ. Chimeric antigen receptor-engineered natural killer and natural killer T cells for cancer immunotherapy. Transl Res. 2017;187:32–43. https://doi.org/10.1016/jtrsl2017.06.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Oelsner S, Friede ME, Zhang C, et al. Continuously expanding CAR NK-92 cells display selective cytotoxicity against B-cell leukemia and lymphoma. Cytotherapy. 2017;19:235–49. https://doi.org/10.1016/jjcyt2016.10.009.

    Article  CAS  PubMed  Google Scholar 

  44. Iliopoulou EG, Kountourakis P, Karamouzis MV, et al. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. Cancer Immunol Immunother. 2010;59:1781–9. https://doi.org/10.1007/s00262-010-0904-3.

    Article  PubMed  Google Scholar 

  45. Schonfeld K, Sahm C, Zhang C, et al. Selective inhibition of tumor growth by clonal NK-cells expressing an ErbB2/HER2-specific chimeric antigen receptor. Mol Ther. 2015;23:330–8. https://doi.org/10.1038/mt2014219.

    Article  PubMed  Google Scholar 

  46. Sakamoto M, Nakajima J, Murakawa T, et al. Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded gammadelta T cells: a phase I clinical study. J Immunother. 2011;34:202–11. https://doi.org/10.1097/CJI0b013e318207ecfb.

    Article  CAS  PubMed  Google Scholar 

  47. Nakajima J, Murakawa T, Fukami T, et al. A phase I study of adoptive immunotherapy for recurrent non-small-cell lung cancer patients with autologous gammadelta T-cells. Eur J Cardiothorac Surg. 2010;37:1191–7. https://doi.org/10.1016/jejcts.2009.11.051.

    Article  PubMed  Google Scholar 

  48. Beatty GL, Haas AR, Maus MV, et al. Mesothelin-specific chimeric antigen receptor mRNA-engineered T-cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res. 2014;2:112–20.

    CAS  PubMed  Google Scholar 

  49. Thistlethwaite FC, Gilham DE, Guest RD, et al. The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T-cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity. Cancer Immunol Immunother. 2017;66:1425–36. https://doi.org/10.1007/s00262-017-2034-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Motohashi S, Ishikawa A, Ishikawa E, et al. A phase I study of in vitro expanded natural killer T-cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res. 2006;12:6079–86. https://doi.org/10.1158/1078-0432CCR-06-0114.

    Article  CAS  PubMed  Google Scholar 

  51. Tonn T, Schwabe D, Klingemann HG, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15:1563–70. https://doi.org/10.1016/jjcyt2013.06.017.

    Article  CAS  PubMed  Google Scholar 

  52. Perroud MW, Honma HN Jr, Barbeiro AS, et al. Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study. J Exp Clin Cancer Res. 2011;30:65. https://doi.org/10.1186/1756-9966-30-65.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Um SJ, Choi YJ, Shin HJ, et al. Phase I study of autologous dendritic cell tumor vaccine in patients with non-small cell lung cancer. Lung Cancer. 2010;70:188–94. https://doi.org/10.1016/jlungcan.2010.02.006.

    Article  PubMed  Google Scholar 

  54. Hu RH, Shi SB, Qi JL, et al. Pemetrexed plus dendritic cells as second-line treatment for patients with stage IIIB/IV non-small cell lung cancer who had treatment with TKI. Med Oncol. 2014;31:63. https://doi.org/10.1007/s12032-014-0063-z.

    Article  CAS  PubMed  Google Scholar 

  55. Zhong R, Teng J, Han B, Zhong H. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol Immunother. 2011;60:1497–502. https://doi.org/10.1007/s00262-011-1060-0.

    Article  CAS  PubMed  Google Scholar 

  56. Zhu XP, Xu YH, Zhou J, Pan XF. A clinical study evaluating dendritic and cytokine-induced killer cells combined with concurrent radiochemotherapy for stage IIIB non-small cell lung cancer. Genet Mol Res. 2015;14:10228–35. https://doi.org/10.4238/2015.

    Article  PubMed  Google Scholar 

  57. Ma J, Liu H, Wang X. Effect of ginseng polysaccharides and dendritic cells on the balance of Th1/Th2 T helper cells in patients with non-small cell lung cancer. J Tradit Chin Med. 2014;34:641–5.

    PubMed  Google Scholar 

  58. Kimura H, Matsui Y, Ishikawa A, Nakajima T, Iizasa T. Randomized controlled phase III trial of adjuvant chemoimmunotherapy with activated cytotoxic T-cells and dendritic cells from regional lymph nodes of patients with lung cancer. Cancer Immunol Immunother. 2018;67:1231–8. https://doi.org/10.1007/s00262-018-2180-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Kimura H, Matsui Y, Ishikawa A, Nakajima T, Yoshino M, Sakairi Y. Randomized controlled phase III trial of adjuvant chemo-immunotherapy with activated killer T-cells and dendritic cells in patients with resected primary lung cancer. Cancer Immunol Immunother. 2015;64:51–9. https://doi.org/10.1007/s00262-014-1613.

    Article  CAS  PubMed  Google Scholar 

  60. Iclozan C, Antonia S, Chiappori A, Chen DT, Gabrilovich D. Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer. Cancer Immunol Immunother. 2013;62:909–18. https://doi.org/10.1007/s00262-013-1396-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Saka H, Kitagawa C, Ichinose Y, et al. A randomized phase II study to assess the effect of adjuvant immunotherapy using alpha-GalCer-pulsed dendritic cells in the patients with completely resected stage II-IIIA non-small cell lung cancer: study protocol for a randomized controlled trial. Trials. 2017;18:429.

    PubMed  PubMed Central  Google Scholar 

  62. Garrido F, Aptsiauri N, Doorduijn EM, Garcia Lora AM, van Hall T. The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr Opin Immunol. 2016;39:44–51. https://doi.org/10.1016/jcoi.2015.12.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Himmel ME, MacDonald KG, Garcia RV, Steiner TS, Levings MK. Helios+ and Helios- cells coexist within the natural FOXP3+ T regulatory cell subset in humans. J Immunol. 2013;190:2001–8. https://doi.org/10.4049/jimmunol.1201379.

    Article  CAS  PubMed  Google Scholar 

  64. Ward-Hartstonge KA, Kemp RA. Regulatory T-cell heterogeneity and the cancer immune response. Clin Transl Immunology. 2017;6:e154. https://doi.org/10.1038/cti.2017.43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kim HR, Park HJ, Son J, et al. Tumor microenvironment dictates regulatory T cell phenotype: Upregulated immune checkpoints reinforce suppressive function. J Immunother Cancer. 2019;7:339. https://doi.org/10.1186/s40425-019-0785-8.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Bruno A, Mortara L, Baci D, Noonan DM, Albini A. Myeloid derived suppressor cells interactions with natural killer cells and pro-angiogenic activities: roles in tumor progression. Front Immunol. 2019;10:771. https://doi.org/10.3389/fimmu.2019.00771.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Choi JN, Sun EG, Cho SH. IL-12 enhances immune response by modulation of myeloid derived suppressor cells in tumor microenvironment. Chonnam Med J. 2019;55:31–9. https://doi.org/10.4068/cmj.2019.55.1.31.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Hanson EM, Clements VK, Sinha P, Ilkovitch D, Ostrand-Rosenberg S. Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J Immunol. 2009;183:937–44. https://doi.org/10.4049/jimmunol.0804253.

    Article  CAS  PubMed  Google Scholar 

  69. Rodriguez PC, Ochoa AC, Al-Khami AA. Arginine metabolism in myeloid cells shapes innate and adaptive immunity. Front Immunol. 2017;8:93. https://doi.org/10.3389/fimmu.2017.00093.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chen Y, Song Y, Du W, Gong L, Chang H, Zou Z. Tumor-associated macrophages: an accomplice in solid tumor progression. J Biomed Sci. 2019;26:78. https://doi.org/10.1186/s12929-019-0568-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Jiang Y, Li Y, Zhu B. T-cell exhaustion in the tumor microenvironment. Cell Death Dis. 2015;6:e1792. https://doi.org/10.1038/cddis2015162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kroemer G, Galluzzi L. Immunotherapy of hematological cancers: PD-1 blockade for the treatment of Hodgkin’s lymphoma. Oncoimmunology. 2015;4:e1008853. https://doi.org/10.1080/2162402X20151008853.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Kudinov AE, Deneka A, Nikonova AS, et al. Musashi-2 (MSI2) supports TGF-beta signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis. Proc Natl Acad Sci U S A. 2016;113:6955–60. https://doi.org/10.1073/pnas.1513616113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wu DM, Deng SH, Liu T, Han R, Zhang T, Xu Y. TGF-beta-mediated exosomal lnc-MMP2-2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression. Cancer Med. 2018;7:5118–29. https://doi.org/10.1002/cam4.1758.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Travis MA, Sheppard D. TGF-beta activation and function in immunity. Annu Rev Immunol. 2014;32:51–82. https://doi.org/10.1146/annurev-immunol-032713-120257.

    Article  CAS  PubMed  Google Scholar 

  76. Liu Y, Cao X. Immunosuppressive cells in tumor immune escape and metastasis. J Mol Med (Berl). 2016;94:509–22. https://doi.org/10.1007/s00109-015-1376-x.

    Article  CAS  Google Scholar 

  77. Abediankenari S, Ghasemi M. Generation of immune inhibitory dendritic cells and CD4+T regulatory cells inducing by TGF-beta. Iran J Allergy Asthma Immunol. 2009;8:25–30.

    CAS  PubMed  Google Scholar 

  78. Mocellin S, Marincola FM, Young HA. Interleukin-10 and the immune response against cancer: a counterpoint. J Leukoc Biol. 2005;78:1043–51. https://doi.org/10.1189/jlb0705358.

    Article  CAS  PubMed  Google Scholar 

  79. Sun Y, Jin X, Liu X, et al. MicroRNA let-7i regulates dendritic cells maturation targeting interleukin-10 via the Janus kinase 1-signal transducer and activator of transcription 3 signal pathway subsequently induces prolonged cardiac allograft survival in rats. J Heart Lung Transplant. 2016;35:378–88. https://doi.org/10.1016/jhealun2015.10.041.

    Article  PubMed  Google Scholar 

  80. Gil-Torregrosa BC, Lennon-Dumenil AM, Kessler B, et al. Control of cross-presentation during dendritic cell maturation. Eur J Immunol. 2004;34:398–407. https://doi.org/10.1002/eji200324508.

    Article  CAS  PubMed  Google Scholar 

  81. Huang FP, Chen YX, To CK. Guiding the “misguided” - functional conditioning of dendritic cells for the DC-based immunotherapy against tumors. Eur J Immunol. 2011;41:18–25. https://doi.org/10.1002/eji201040543.

    Article  CAS  PubMed  Google Scholar 

  82. Liu B, Qu L, Yan S. Cyclooxygenase-2 promotes tumor growth and suppresses tumor immunity. Cancer Cell Int. 2015;15:106. https://doi.org/10.1186/s12935-015-0260-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. van Baren N, Van den Eynde BJ. Tumoral immune resistance mediated by enzymes that degrade tryptophan. Cancer Immunol Res. 2015;3:978–85. https://doi.org/10.1158/2326-6066.CIR-15-0095.

    Article  CAS  PubMed  Google Scholar 

  84. Trabanelli S, Lecciso M, Salvestrini V, et al. PGE2-induced IDO1 inhibits the capacity of fully mature DCs to elicit an in vitro antileukemic immune response. J Immunol Res. 2015;2015:253191. https://doi.org/10.1155/2015/253191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Trabanelli S, Ocadlikova D, Ciciarello M, et al. The SOCS3-independent expression of IDO2 supports the homeostatic generation of T regulatory cells by human dendritic cells. J Immunol. 2014;192:1231–40. https://doi.org/10.4049/jimmunol.1300720.

    Article  CAS  PubMed  Google Scholar 

  86. Hack K, Reilly L, Proby C, Fleming C, Leigh I, Foerster J. Wnt5a inhibits the CpG oligodeoxynucleotide-triggered activation of human plasmacytoid dendritic cells. Clin Exp Dermatol. 2012;37:557–61. https://doi.org/10.1111/j1365.2230.201204362.x.

    Article  CAS  PubMed  Google Scholar 

  87. Fang Y, Kang Y, Zou H, et al. Beta-elemene attenuates macrophage activation and proinflammatory factor production via crosstalk with Wnt/beta-catenin signaling pathway. Fitoterapia. 2018;124:92–102. https://doi.org/10.1016/jfitote.2017.10.015.

    Article  CAS  PubMed  Google Scholar 

  88. Valencia J, Hernandez-Lopez C, Martinez VG, et al. Wnt5a skews dendritic cell differentiation to an unconventional phenotype with tolerogenic features. J Immunol. 2011;187:4129–39. https://doi.org/10.4049/jimmunol.1101243.

    Article  CAS  PubMed  Google Scholar 

  89. Hong Y, Manoharan I, Suryawanshi A, et al. Beta-catenin promotes regulatory T-cell responses in tumors by inducing vitamin a metabolism in dendritic cells. Cancer Res. 2015;75:656–65. https://doi.org/10.1158/0008-5472.CAN-14-2377.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Holtzhausen A, Zhao F, Evans KS, et al. Melanoma-derived Wnt5a promotes local dendritic-cell expression of IDO and immunotolerance: opportunities for pharmacologic enhancement of immunotherapy. Cancer Immunol Res. 2015;3:1082–95. https://doi.org/10.1158/2326-6066.CIR-14-0167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Muller AJ, Manfredi MG, Zakharia Y, Prendergast GC. Inhibiting IDO pathways to treat cancer: lessons from the ECHO-301 trial and beyond. Semin Immunopathol. 2019;41:41–8. https://doi.org/10.1007/s00281-018-0702-0.

    Article  CAS  PubMed  Google Scholar 

  92. Amreddy N, Babu A, Muralidharan R, Munshi A, Ramesh R. Polymeric nanoparticle-mediated gene delivery for lung cancer treatment. Top Curr Chem (Cham). 2017;375:35. https://doi.org/10.1007/s41061-017-0128-5.

    Article  CAS  Google Scholar 

  93. Mangal S, Gao W, Li T, Zhou QT. Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities. Acta Pharmacol Sin. 2017;38:782–97. https://doi.org/10.1038/aps.2017.34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Jain D, Jain V, Singh R. Novel antigen delivery technologies: a review. Drug Deliv Transl Res. 2011;1:103–12. https://doi.org/10.1007/s13346-011-0014-6.

    Article  CAS  PubMed  Google Scholar 

  95. Chen H, Zeng Y, Liu W, Zhao S, Wu J, Du Y. Multifaceted applications of nanomaterials in cell engineering and therapy. Biotechnol Adv. 2013;31:638–53.

    CAS  PubMed  Google Scholar 

  96. Swetha KL, Roy A. Tumor heterogeneity and nanoparticle-mediated tumor targeting: the importance of delivery system personalization. Drug Deliv Transl Res. 2018;8:1508–26. https://doi.org/10.1007/s13346-018-0578-5.

    Article  CAS  PubMed  Google Scholar 

  97. Yu W, Liu C, Liu Y, Zhang N, Xu W. Mannan-modified solid lipid NPs for targeted gene delivery to alveolar macrophages. Pharm Res. 2010;27:1584–96. https://doi.org/10.1007/s11095-010-0149-z.

    Article  CAS  PubMed  Google Scholar 

  98. Kaur A, Jyoti K, Rai S, et al. Tetanus toxoid-loaded cationic non-aggregated nanostructured lipid particles triggered strong humoral and cellular immune responses. J Microencapsul. 2016;33:263–73. https://doi.org/10.3109/02652048.2016.1169324.

    Article  CAS  PubMed  Google Scholar 

  99. Li P, Zhou J, Huang P, et al. Self-assembled PEG-b-PDPA-b-PGEM copolymer NPs as protein antigen delivery vehicles to dendritic cells: preparation, characterization and cellular uptake. Regen Biomater. 2017;4:11–20. https://doi.org/10.1093/rb/rbw044.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Chen X, Liu Y, Wang L, et al. Enhanced humoral and cell-mediated immune responses generated by cationic polymer-coated PLA microspheres with adsorbed HBsAg. Mol Pharm. 2014;11:1772–84. https://doi.org/10.1021/mp400597z.

    Article  CAS  PubMed  Google Scholar 

  101. Schmid D, Park CG, Hartl CA, et al. T-cell-targeting NPs focus delivery of immunotherapy to improve antitumor immunity. Nat Commun. 2017;8:1747. https://doi.org/10.1038/s41467-017-01830-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Duong HTT, Kim NW, Thambi T, et al. Microneedle arrays coated with charge reversal pH-sensitive copolymers improve antigen presenting cells-homing DNA vaccine delivery and immune responses. J Control Release. 2018;269:225–34. https://doi.org/10.1016/jjconrel.2017.11.025.

    Article  CAS  PubMed  Google Scholar 

  103. Brinkhoff B, Ostroumov D, Heemcke J, et al. Microsphere priming facilitates induction of potent therapeutic T-cell immune responses against autochthonous liver cancers. Eur J Immunol. 2014;44:1213–24. https://doi.org/10.1002/eji.201343794.

    Article  CAS  PubMed  Google Scholar 

  104. Li HS, Singh B, Park TE, et al. Mannan-decorated thiolated Eudragit microspheres for targeting antigen presenting cells via nasal vaccination. Eur J Immunol. 2015;80:16–25. https://doi.org/10.1016/jejps201509014.

    Article  Google Scholar 

  105. Vang KB, Safina I, Darrigues E, et al. Modifying dendritic cell activation with plasmonic nano vectors. Sci Rep. 2017;7:5513. https://doi.org/10.1038/s41598-017-04459-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Liang R, Xie J, Li J, et al. Liposomes-coated gold nanocages with antigens and adjuvants targeted delivery to dendritic cells for enhancing antitumor immune response. Biomaterials. 2017;149:41–50. https://doi.org/10.1016/jbiomaterials.2017.09.029.

    Article  CAS  PubMed  Google Scholar 

  107. Climent N, Garcia I, Marradi M, et al. Loading dendritic cells with gold NPs (GNPs) bearing HIV-peptides and mannosides enhance HIV-specific T-cell responses. Nanomedicine. 2018;14:339–51. https://doi.org/10.1016/jnano.2017.11.009.

    Article  CAS  PubMed  Google Scholar 

  108. Nam J, Son S, Moon JJ. Adjuvant-loaded spiky gold NPs for activation of innate immune cells. Cell Mol Bioeng. 2017;10:341–55. https://doi.org/10.1007/s12195-017-0505-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Zhao Y, Zhao X, Cheng Y, Guo X, Yuan W. Iron oxide NPs-based vaccine delivery for cancer treatment. Mol Pharm. 2018;15:1791–9. https://doi.org/10.1021/acsmolpharmaceut.7b01103.

    Article  CAS  PubMed  Google Scholar 

  110. Zhang P, Chiu YC, Tostanoski LH, Jewell CM. Polyelectrolyte multilayers assembled entirely from immune signals on gold NP templates promote antigen-specific T-cell response. ACS Nano. 2015;9:6465–77. https://doi.org/10.1021/acsnano.5b02153.

    Article  CAS  PubMed  Google Scholar 

  111. Wu L, Wang Z, Zhang Y, et al. In situ probing of cell–cell communications with surface-enhanced Raman scattering (SERS) nanoprobes and microfluidic networks for screening of immunotherapeutic drugs. Nano Res. 2017;10:584–94. https://doi.org/10.1007/s12274-016-1316-2.

    Article  CAS  Google Scholar 

  112. Chiang CS, Lin YJ, Lee R, et al. Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumor-localized immunotherapy. Nat Nanotechnol. 2018;13:746–54. https://doi.org/10.1038/s41565-018-0146-7.

    Article  CAS  PubMed  Google Scholar 

  113. Nawwab Al-Deen FM, Selomulya C, Kong YY, et al. Design of magnetic polyplexes taken up efficiently by dendritic cell for enhanced DNA vaccine delivery. Gene Ther. 2014;21:212–8. https://doi.org/10.1038/gt2013.77.

    Article  CAS  PubMed  Google Scholar 

  114. Cho NH, Cheong TC, Min JH, et al. A multifunctional core-shell NP for dendritic cell-based cancer immunotherapy. Nat Nanotechnol. 2011;6:675–82. https://doi.org/10.1038/nnano.2011.149.

    Article  CAS  PubMed  Google Scholar 

  115. Zilio S, Vella JL, De la Fuente AC, et al. 4PD functionalized dendrimers: a flexible tool for in vivo gene silencing of tumor-educated myeloid cells. J Immunol. 2017;198:4166–77. https://doi.org/10.4049/jimmunol1600833.

    Article  CAS  PubMed  Google Scholar 

  116. Chahal JS, Khan OF, Cooper CL, et al. Dendrimer-RNA NPs generate protective immunity against lethal Ebola, H1N1 influenza, and toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci U S A. 2016;113:E4133–42. https://doi.org/10.1073/pnas.1600299113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Aldinucci A, Turco A, Biagioli T, et al. Carbon nanotube scaffolds instruct human dendritic cells: modulating immune responses by contacts at the nanoscale. Nano Lett. 2013;13:6098–105. https://doi.org/10.1021/nl403396e.

    Article  CAS  PubMed  Google Scholar 

  118. Sinha A, Cha BG, Choi Y, et al. Carbohydrate-functionalized rGO as an effective cancer vaccine for stimulating antigen-specific cytotoxic T-cells and inhibiting tumor growth. Chem Mater. 2017;29:6883–92. https://doi.org/10.1021/acs.chemmater.7b02197.

    Article  CAS  Google Scholar 

  119. Tao Y, Ju E, Ren J, Qu X. Immunostimulatory oligonucleotides-loaded cationic graphene oxide with photothermally enhanced immunogenicity for photothermal/immune cancer therapy. Biomaterials. 2014;35:9963–71. https://doi.org/10.1016/jbiomaterials.201408036.

    Article  CAS  PubMed  Google Scholar 

  120. Chiu YC, Gammon JM, Andorko JI, Tostanoski LH, Jewell CM. Modular vaccine design using carrier-free capsules assembled from polyionic immune signals. ACS Biomater Sci Eng. 2015;1:1200–5. https://doi.org/10.1021/acsbiomaterials5b00375.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Lee HY, Mohammed KA, Nasreen N. Nanoparticle-based targeted gene therapy for lung cancer. Am J Cancer Res. 2016;6:1118–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60:1615–26. https://doi.org/10.1016/j.addr.2008.08.005.

    Article  CAS  PubMed  Google Scholar 

  123. Karra N, Benita S. The ligand nanoparticle conjugation approach for targeted cancer therapy. Curr Drug Metab. 2012;13:22–41. https://doi.org/10.2174/138920012798356899.

    Article  CAS  PubMed  Google Scholar 

  124. Bazak R, Houri M, El Achy S, Kamel S, Refaat T. Cancer active targeting by nanoparticles: a comprehensive review of literature. J Cancer Res Clin Oncol. 2015;141:769–84. https://doi.org/10.1007/s00432-014-1767-3.

    Article  CAS  PubMed  Google Scholar 

  125. Babu A, Templeton AK, Munshi A, Ramesh R. Nanoparticle-based drug delivery for therapy of lung cancer: progress and challenges. J Nanomater. 2013;863951:11. https://doi.org/10.1155/2013/863951.

    Article  CAS  Google Scholar 

  126. Park W, Heo YJ, Han DK. New opportunities for nanoparticles in cancer immunotherapy. Biomater Res. 2018;22:24. https://doi.org/10.1186/s40824-018-0133-y eCollection 2018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Velpurisiva P, Gad A, Piel B, Jadia R, Rai P. Nanoparticle design strategies for effective cancer immunotherapy. J Biomed (Syd). 2017;2:64–77. https://doi.org/10.7150/jbm.18877.

    Article  Google Scholar 

  128. Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K. Potentiation of pH-sensitive polymer-modified liposomes with cationic lipid inclusion as antigen delivery carriers for cancer immunotherapy. Biomaterials. 2014;35:8186–96. https://doi.org/10.1016/jbiomaterials201405077.

    Article  CAS  PubMed  Google Scholar 

  129. Bhargava A, Mishra D, Banerjee S, Mishra PK. Engineered dendritic cells for gastrointestinal tumor immunotherapy: opportunities in translational research. J Drug Target. 2013;21:126–36. https://doi.org/10.3109/1061186X.2012.731069.

    Article  CAS  PubMed  Google Scholar 

  130. Nascimento TL, Hillaireau H, Vergnaud J, Fattal E. Lipid-based nanosystems for CD44 targeting in cancer treatment: recent significant advances, ongoing challenges and unmet needs. Nanomedicine (London). 2016;11:1865–87. https://doi.org/10.2217/nnm-2016-5000.

    Article  CAS  Google Scholar 

  131. Dhas NL, Kudarha RR, Acharya NS, Acharya SR. Polymeric immunonps mediated cancer therapy: versatile nanocarriers for cell-specific cargo delivery. Crit Rev Ther Drug Carrier Syst. 2018;35:1–64. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2017018714.

    Article  PubMed  Google Scholar 

  132. Kosmides AK, Necochea K, Hickey JW, Schneck JP. Separating T-cell targeting components onto magnetically clustered NPs boosts activation. Nano Lett. 2018;18:1916–24. https://doi.org/10.1021/acs.nanolett7b05284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Muthukumarasamyvel T, Rajendran G, Santhana Panneer D, Kasthuri J, Kathiravan K, Rajendiran N. Role of surface hydrophobicity of dicationic amphiphile-stabilized gold NPs on A549 lung cancer cells. ACS Omega. 2017;2:3527–38. https://doi.org/10.1021/acsomega.7b00353.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Dai L, Yu Y, Luo Z, et al. Photosensitizer enhanced disassembly of amphiphilic micelle for ROS-response targeted tumor therapy in vivo. Biomaterials. 2016;104:1–17. https://doi.org/10.1016/jbiomaterials.201607002.

    Article  CAS  PubMed  Google Scholar 

  135. Saleem J, Wang L, Chen C. Carbon-based nanomaterials for cancer therapy via targeting tumor microenvironment. Adv Healthc Mater. 2018;7:e1800525. https://doi.org/10.1002/adhm201800525.

    Article  PubMed  Google Scholar 

  136. Sanz-Ortega L, Rojas JM, Portilla Y, Pérez-Yagüe S, Barber DF. Magnetic nanoparticles attached to the NK cell surface for tumor targeting in adoptive transfer therapies does not affect cellular effector functions. Front Immunol. 2019;10:2073. https://doi.org/10.3389/fimmu.2019.02073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Mishra D, Mishra PK, Dubey V, Dabadghao S, Jain NK. Evaluation of uptake and generation of immune response by murine dendritic cells pulsed with hepatitis B surface antigen-loaded elastic liposomes. Vaccine. 2007;25:6939–44. https://doi.org/10.1016/jvaccine200706055.

    Article  CAS  PubMed  Google Scholar 

  138. Mizrahy S, Hazan-Halevy I, Landesman-Milo D, Ng BD, Peer D. Advanced strategies in immune modulation of cancer using lipid-based NPs. Front Immunol. 2017;8:69. https://doi.org/10.3389/fimmu.2017.00069.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Mishra DK, Shandilya R, Mishra PK. Lipid based nanocarriers: a translational perspective. Nanomedicine. 2018;14:2023–50. https://doi.org/10.1016/jnano201805021.

    Article  CAS  PubMed  Google Scholar 

  140. Jyoti K, Kaur K, Pandey RS, Jain UK, Chandra R, Madan J. Inhalable nanostructured lipid particles of 9-bromo-noscapine, a tubulin-binding cytotoxic agent: in vitro and in vivo studies. Colloid Interface Sci. 2015;445:219–30.

    CAS  Google Scholar 

  141. Sun L, Wan K, Hu X, et al. Functional nanoemulsion-hybrid lipid nanocarriers enhance the bioavailability and anti-cancer activity of lipophilic diferuloylmethane. Nanotechnology. 2016;27:085102.

    PubMed  Google Scholar 

  142. Wan K, Sun L, Hu X, et al. Novel nanoemulsion based lipid nanosystems for favorable in vitro and in vivo characteristics of curcumin. Int J Pharm. 2016;504:80–8.

    CAS  PubMed  Google Scholar 

  143. Asmawi AA, Salim N, Ngan CL, et al. Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment. Drug Deliv Transl Res. 2018;9:543–54.

    Google Scholar 

  144. García-Pinel B, Porras-Alcalá C, Ortega-Rodríguez A, et al. Lipid-based nanoparticles: application and recent advances in cancer treatment. Nanomaterials (Basel). 2019;9:E638. https://doi.org/10.3390/nano.9040638.

    Article  Google Scholar 

  145. Mishra D, Mishra PK, Dabadghao S, Dubey V, Nahar M, Jain NK. Comparative evaluation of hepatitis B surface antigen-loaded elastic liposomes and ethosomes for human dendritic cell uptake and immune response. Nanomedicine. 2010;6:110–8. https://doi.org/10.1016/jnano200904003.

    Article  CAS  PubMed  Google Scholar 

  146. Zanganeh S, Xu Y, Hamby CV, Backer MV, Backer JM, Zhu Q. Enhanced fluorescence diffuse optical tomography with indocyanine green-encapsulating liposomes targeted to receptors for vascular endothelial growth factor in tumor vasculature. J Biomed Opt. 2013;18:126014. https://doi.org/10.1117/1JBO1812126014.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Butts C, Maksymiuk A, Goss G, et al. Updated survival analysis in patients with stage IIIB or IV non-small-cell lung cancer receiving BLP25 liposome vaccine (L-BLP25): phase IIB randomized, multicenter, open-label trial. J Cancer Res Clin Oncol. 2011;137:1337–42. https://doi.org/10.1007/s00432-011-1003-3.

    Article  CAS  PubMed  Google Scholar 

  148. Ektate K, Munteanu MC, Ashar H, Malayer J, Ranjan A. Chemo-immunotherapy of colon cancer with focused ultrasound and Salmonella-laden temperature sensitive liposomes (thermobots). Sci Rep. 2018;8:13062. https://doi.org/10.1038/s41598-018-30106-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Bartheldyova E, Effenberg R, Masek J, et al. Hyaluronic acid surface modified liposomes prepared via orthogonal aminoxy coupling: synthesis of nontoxic aminoxylipids based on symmetrically alpha-branched fatty acids, preparation of liposomes by microfluidic mixing, and targeting to cancer cells expressing CD44. Bioconjug Chem. 2018;29:2343–56. https://doi.org/10.1021/acsbioconjchem8b00311.

    Article  CAS  PubMed  Google Scholar 

  150. Zhang JL, Srivastava RS, Misra RD. Core-shell magnetite NPs surface encapsulated with smart stimuli-responsive polymer: synthesis, characterization, and LCST of viable drug-targeting delivery system. Langmuir. 2007;23:6342–51.

    CAS  PubMed  Google Scholar 

  151. Gogoi M, Kumar N, Patra, S In Nanoarchitectonics for smart delivery and -drug targeting (Eds A M Holban, A M Grumezescu,), William Andrew Publishing: Norwich, 2016, 743–782, ISBN 978-0-323-47347-7.

  152. Kunjachan S, Ehling J, Storm G, Kiessling F, Lammers T. Noninvasive imaging of nanomedicines and nanotheranostics: principles, Progress, and Prospects. Chem Rev. 2015;115:10907–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Cheng L, Huang FZ, Cheng LF, et al. GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation. Int J Nanomedicine. 2014;9:921–35.

    PubMed  PubMed Central  Google Scholar 

  154. Lin C, Zhang X, Chen H, et al. Dual-ligand modified liposomes provide effective local targeted delivery of lung-cancer drug by antibody and tumor lineage-homing cell-penetrating peptide. Drug Deliv. 2018;25:256–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Song XL, Ju RJ, Xiao Y, et al. Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer. Int J Nanomedicine. 2017;12:7433–51.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Ganesan P, Ramalingam P, Karthivashan G, Ko YT, Choi DK. Recent developments in solid lipid NP and surface-modified solid lipid NP delivery systems for oral delivery of phyto-bioactive compounds in various chronic diseases. Int J Nanomedicine. 2018;13:1569–83. https://doi.org/10.2147/IJN.S155593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Pindiprolu SKSS, Chintamaneni PK, Krishnamurthy PT, Ratna Sree Ganapathineedi K. Formulation-optimization of solid lipid nanocarrier system of STAT3 inhibitor to improve its activity in triple negative breast cancer cells. Drug Dev Ind Pharm. 2018;45:304–13.

    PubMed  Google Scholar 

  158. Eskiler GG. Synthetically lethal BMN 673 (Talazoparib) loaded solid lipid nanoparticles for BRCA1 mutant triple negative breast cancer. Pharm Res. 2018;35:218.

    Google Scholar 

  159. Oliveira RR, Carrião MS, Pacheco MT, et al. Triggered release of paclitaxel from magnetic solid lipid nanoparticles by magnetic hyperthermia. Mater Sci Eng C. 2018;92:547–53.

    CAS  Google Scholar 

  160. Wang W, Zhang L, Chen T, et al. Anticancer effects of resveratrol-loaded solid lipid nanoparticles on human breast cancer cells. Molecules. 2017;22:1814.

    PubMed Central  Google Scholar 

  161. Chirio D, Peira E, Battaglia L, et al. Lipophilic prodrug of floxuridine loaded into solid lipid nanoparticles: in vitro cytotoxicity studies on different human cancer cell lines. Nanosci Nanotechnol. 2018;18:556–63.

    CAS  Google Scholar 

  162. Rosière R, Van Woensel M, Gelbcke M, et al. New folate-grafted chitosan derivative to improve delivery of paclitaxel-loaded solid lipid nanoparticles for lung tumor therapy by inhalation. Mol Pharm. 2018;15:899–910.

    PubMed  Google Scholar 

  163. Fahmy UA. Augmentation of Fluvastatin cytotoxicity against prostate carcinoma PC3 cell line utilizing alpha lipoic–ellagic acid nanostructured lipid carrier formula. AAPS PharmSciTech. 2018;19:3454–61.

    CAS  PubMed  Google Scholar 

  164. Haron AS, Syed Alwi SS, Saiful Yazan L, et al. Cytotoxic effect of thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) on liver cancer cell integrated with hepatitis B genome, Hep3B. Evid Based Complement Alternat Med. 2018;2018:1549805.

    PubMed  PubMed Central  Google Scholar 

  165. Li J, Jin S, Dong XR, Han XF, Wang MY. Construction of artesunate nanoparticles modified by hyaluronic acid and cell-penetrating peptides and its inhibitory effect on cancer cells in vitro. China J Chin Mater Med. 2018;43:3668–75.

    Google Scholar 

  166. Nahak P, Gajbhiye RL, Karmakar G, et al. Orcinol glucoside loaded polymer-lipid hybrid nanostructured lipid carriers: potential cytotoxic agents against gastric Colon and Hepatoma Carcinoma Cell Lines. Pharm Res. 2018;35:198.

    PubMed  Google Scholar 

  167. Wei Q, Yang Q, Wang Q, et al. Formulation, characterization, and pharmacokinetic studies of 6-gingerol-loaded nanostructured lipid carriers. AAPS Pharm Sci Tech. 2018;19:3661–9.

    CAS  Google Scholar 

  168. Ghaffari M, Dehghan G, Abedi-Gaballu F, et al. Surface functionalized dendrimers as controlled-release delivery nanosystems for tumor targeting. Eur J Pharm Sci. 2018;122:311–30. https://doi.org/10.1016/jejps201807020.

    Article  CAS  PubMed  Google Scholar 

  169. Shadrack DM, Swai HS, Munissi JJE, Mubofu EB, Nyandoro SS. Polyamidoamine dendrimers for enhanced solubility of small molecules and other desirable properties for site specific delivery: insights from experimental and computational studies. Molecules. 2018;23:E1419. https://doi.org/10.3390/molecules23061419.

    Article  CAS  PubMed  Google Scholar 

  170. Liu J, Liu J, Chu L, et al. Novel peptide-dendrimer conjugates as drug carriers for targeting nonsmall cell lung cancer, conjugates as drug carriers for targeting nonsmall cell lung cancer. Int J Nanomedicine. 2010;6:59–69.

    CAS  PubMed  PubMed Central  Google Scholar 

  171. Ryan GM, Kaminskas LM, Kelly BD, et al. Pulmonary administration of PEGylated polylysine dendrimers: absorption from the lung versus retention within the lung is highly size-dependent. Mol Pharm. 2013;10:2986–95.

    CAS  PubMed  Google Scholar 

  172. Kaminskas LM, McLeod VM, Ryan GM, et al. Pulmonary administration of a doxorubicin-conjugated dendrimer enhances drug exposure to lung metastases and improves cancer therapy. J Control Release. 2014;183:18–26.

    CAS  PubMed  Google Scholar 

  173. Hasanzadeh M, Babaie P, Jouyban-Gharamaleki V, Jouyban A. The use of chitosan as a bioactive polysaccharide in non-invasive detection of malondialdehyde biomarker in human exhaled breath condensate: a new platform towards diagnosis of some lung disease. Int J Biol Macromol. 2018;120(Pt B):2482–92. https://doi.org/10.1016/jijbiomac.2018.09.018.

    Article  CAS  PubMed  Google Scholar 

  174. Shirvalilou S, Khoei S, Khoee S, Raoufi NJ, Karimi MR, Shakeri-Zadeh A. Development of a magnetic nano-graphene oxide Carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations. Chem Biol Interact. 2018;S0009–2797:30160–1. https://doi.org/10.1016/jcbi.2018.08.027.

    Article  Google Scholar 

  175. Niikura K, Matsunaga T, Suzuki T, et al. Gold NPs as a vaccine platform: influence of size and shape on immunological responses in vitro and in vivo. ACS Nano. 2013;7:3926–38. https://doi.org/10.1021/nn3057005.

    Article  CAS  PubMed  Google Scholar 

  176. Kim YH, Min KH, Wang Z, et al. Development of sialic acid-coated NPs for targeting cancer and efficient evasion of the immune system. Theranostics. 2017;7:962–73. https://doi.org/10.7150/thno.19061.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Peng G, Tisch U, Adams O, et al. Diagnosing lung cancer in exhaled breath using gold nanoparticles. Nat Nanotechnol. 2009;4:669–73.

    CAS  PubMed  Google Scholar 

  178. Ramalingam V, Varunkumar K, Ravikumar V, Rajaram R. Target delivery of doxorubicin tethered with PVP stabilized gold nanoparticles for effective treatment of lung cancer. Sci Rep. 2018;8:3815.

    PubMed  PubMed Central  Google Scholar 

  179. Kim SW, Lee YK, Lee JY, Hong JH, Khang D. PEGylated anticancer-carbon nanotubes complex targeting mitochondria of lung cancer cells. Nanotechnology. 2017;28:465102.

    PubMed  Google Scholar 

  180. Singh RP, Sharma G, Singh S, et al. Chitosan-folate decorated carbon nanotubes for site specific lung cancer delivery. Mater Sci Eng C. 2017;77:446–58.

    CAS  Google Scholar 

  181. Subramanian A, Manigandan A, Sivashankari PR, Sethuraman S. Development of nanotheranostics against metastatic breast cancer--a focus on the biology & mechanistic approaches. Biotechnol Adv. 2015;33:1897–911. https://doi.org/10.1016/jbiotechadv.2015.10.002.

    Article  PubMed  Google Scholar 

  182. Akhter MH, Rizwanullah M, Ahmad J, Ahsan MJ, Mujtaba MA, Amin S. Nanocarriers in advanced drug targeting: setting novel paradigm in cancer therapeutics. Artif Cells Nanomed Biotechnol. 2018;46:873–84. https://doi.org/10.1080/2169140120171366333.

    Article  CAS  PubMed  Google Scholar 

  183. Danhier F, Feron O, Preat V. To exploit the tumor microenvironment: passive and active tumor targeting of nanocarriers for anti-cancer drug delivery. J Control Release. 2010;148:135–46. https://doi.org/10.1016/jjconrel201008027.

    Article  CAS  PubMed  Google Scholar 

  184. Chen X, Wang Q, Liu L. Double-sided effect of tumor microenvironment on platelets targeting NPs. Biomaterials. 2018;183:258–67. https://doi.org/10.1016/jbiomaterials201807005.

    Article  CAS  PubMed  Google Scholar 

  185. Gao Y, Xie J, Chen H, et al. Nanotechnology-based intelligent drug design for cancer metastasis treatment. Biotechnol Adv. 2014;32:761–77. https://doi.org/10.1016/jbiotechadv201310013.

    Article  CAS  PubMed  Google Scholar 

  186. Hussain Z, Khan S, Imran M, Sohail M, Shah SWA, de Matas M. PEGylation: a promising strategy to overcome challenges to cancer-targeted nanomedicines: a review of challenges to clinical transition and promising resolution. Drug Deliv Transl Res. 2019;9:721–34. https://doi.org/10.1007/s13346-019-00631-4.

    Article  CAS  PubMed  Google Scholar 

  187. Freichels H, Pourcelle V, Auzely-Velty R, Marchand-Brynaert J, Jerome C. Synthesis of poly(lactide-co-glycolide-co-epsilon-caprolactone)-graft-mannosylated poly(ethylene oxide) copolymers by combination of “clip” and “click” chemistries. Biomacromolecules. 2012;13:760–8. https://doi.org/10.1021/bm201690w.

    Article  CAS  PubMed  Google Scholar 

  188. Wesch D, Peters C, Oberg HH, Pietschmann K, Kabelitz D. Modulation of gammadelta T-cell responses by TLR ligands. Cell Mol Life Sci. 2011;68:2357–70. https://doi.org/10.1007/s00018-011-0699-1.

    Article  CAS  PubMed  Google Scholar 

  189. Silva JM, Videira M, Gaspar R, Preat V, Florindo HF. Immune system targeting by biodegradable NPs for cancer vaccines. J Control Release. 2013;168:179–99. https://doi.org/10.1016/jjconrel201303010.

    Article  CAS  PubMed  Google Scholar 

  190. van Kooyk Y. C-type lectins on dendritic cells: key modulators for the induction of immune responses. Biochem Soc Trans. 2008;36:1478–81. https://doi.org/10.1042/BST0361478.

    Article  CAS  PubMed  Google Scholar 

  191. Unger WW, van Kooyk Y. Dressed for success’ C-type lectin receptors for the delivery of glyco-vaccines to dendritic cells. Curr Opin Immunol. 2011;23:131–7. https://doi.org/10.1016/jcoi2010.11011.

    Article  CAS  PubMed  Google Scholar 

  192. Vonderheide RH, Bajor DL, Winograd R, Evans RA, Bayne LJ, Beatty GL. CD40 immunotherapy for pancreatic cancer. Cancer Immunol Immunother. 2013;62:949–54. https://doi.org/10.1007/s00262-013-1427-5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Nicolas J, Mura S, Brambilla D, Mackiewicz N, Couvreur P. Design, functionalization strategies and biomedical applications of targeted biodegradable/biocompatible polymer-based nanocarriers for drug delivery. Chem Soc Rev. 2013;42:1147–235. https://doi.org/10.1039/c2cs35265f.

    Article  CAS  PubMed  Google Scholar 

  194. Bietenbeck M, Florian A, Faber C, Sechtem U, Yilmaz A. PEGylation strategies for active targeting of PLA/PLGA NPs. J Biomed Mater Res A. 2009;91:263–76. https://doi.org/10.1002/jbma32247.

    Article  Google Scholar 

  195. Tatiparti K, Sau S, Gawde KA, et al. Copper-free ‘click’ chemistry-based synthesis and characterization of carbonic anhydrase-IX anchored albumin-paclitaxel NPs for targeting tumor hypoxia. Int J Mol Sci. 2018;19:E838. https://doi.org/10.3390/ijms19030838.

    Article  CAS  PubMed  Google Scholar 

  196. Bhargava A, Bunkar N, Khare NK, Mishra D, Mishra PK. Nanoengineered strategies to optimize dendritic cells for gastrointestinal tumor immunotherapy: from biology to translational medicine. Nanomedicine (London). 2014;9:2187–202. https://doi.org/10.2217/nn.14.115.

    Article  CAS  Google Scholar 

  197. Yan L, Crayton SH, Thawani JP, Amirshaghaghi A, Tsourkas A, Cheng Z. A pH-responsive drug-delivery platform based on glycol chitosan-coated liposomes. Small. 2015;11:4870–4. https://doi.org/10.1002/smll201501412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Kale AA, Torchilin VP. Environment-responsive multifunctional liposomes. Methods Mol Biol. 2010;605:213–42. https://doi.org/10.1007/978-1-60327-360-2_15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Yu MK, Park J, Jon S. Magnetic nanoparticles and their applications in image-guided drug delivery. Drug Deliv Transl Res. 2012;2:3–21. https://doi.org/10.1007/s13346-011-0049-8.

    Article  CAS  PubMed  Google Scholar 

  200. Stephan SB, Taber AM, Jileaeva I, et al. Biopolymer implants enhance the efficacy of adoptive T-cell therapy. Nat Biotechnol. 2015;33:97–101. https://doi.org/10.1038/nbt3104.

    Article  CAS  PubMed  Google Scholar 

  201. Abedin MR, Umapathi S, Mahendrakar H, et al. Polymer coated gold-ferric oxide superparamagnetic nanoparticles for theranostic applications. J Nanobiotechnology. 2018;16:80. https://doi.org/10.1186/s12951-018-0405-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Jauregui R, Srinivasan S, Vojtech LN, et al. Temperature-responsive magnetic NPs for enabling affinity separation of extracellular vesicles. ACS Appl Mater Interfaces. 2018;10:33847–56. https://doi.org/10.1021/acsami8b09751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Wabler M, Zhu W, Hedayati M, et al. Magnetic resonance imaging contrast of iron oxide NPs developed for hyperthermia is dominated by iron content. Int J Hyperthermia. 2014;30:192–200. https://doi.org/10.3109/02656736.2014.913321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Unterweger H, Dezsi L, Matuszak J, et al. Dextran-coated superparamagnetic iron oxide NPs for magnetic resonance imaging: evaluation of size-dependent imaging properties, storage stability and safety. Int J Nanomedicine. 2018;13:1899–915. https://doi.org/10.2147/IJN.S156528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Yang QQ, Wei XL, Fang YP, et al. Nanochemoprevention with therapeutic benefits: an updated review focused on epigallocatechin gallate delivery. Crit Rev Food Sci Nutr. 2019;23:1–22. https://doi.org/10.1080/10408398.2019.1565490.

    Article  CAS  Google Scholar 

  206. Ferguson PM, Slocombe A, Tilley RD, Hermans IF. Using magnetic resonance imaging to evaluate dendritic cell-based vaccination. PLoS One. 2013;8:e65318. https://doi.org/10.1371/journalpone0065318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Gholipourmalekabadi M, Mobaraki M, Ghaffari M, et al. Targeted drug delivery based on gold np derivatives. Curr Pharm Des. 2017;23:2918–29. https://doi.org/10.2174/1381612823666170419105413.

    Article  CAS  PubMed  Google Scholar 

  208. Wallace A, Kapoor V, Sun J, et al. Transforming growth factor-β receptor blockade augments the effectiveness of adoptive T cell therapy of established solid cancers. Clin Cancer Res. 2008;14:3966–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  209. Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov. 2019;18:175–96. https://doi.org/10.1038/s41573-018-0006-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Stephan MT, Moon JJ, Um SH, Bersthteyn A, Irvine DJ. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat Med. 2010;16:1035–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  211. Stephan MT, Stephan SB, Bak P, Chen J, Irvine DJ. Synapse-directed delivery of immunomodulators using T cell-conjugated nanoparticles. Biomaterials. 2012;33:5776–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  212. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human. Cancer Sci. 2015;348:62–8.

    CAS  Google Scholar 

  213. Smith T, Stephan SB, Moffett HF, et al. In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers. Nat Nanotechnol. 2017;12:813–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  214. Smith TT, Moffett HF, Stephan SB, et al. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors. J Clin Invest. 2017;127:2176–91.

    PubMed  PubMed Central  Google Scholar 

  215. Yang S, Wen J, Li H, et al. Aptamer-engineered natural killer cells for cell-specific adaptive immunotherapy. Small. 2019;15:e1900903. https://doi.org/10.1002/smll201900903.

    Article  PubMed  PubMed Central  Google Scholar 

  216. Meyer RA, Sunshine JC, Perica K, et al. Biodegradable nanoellipsoidal artificial antigen presenting cells for antigen specific T-cell activation. Small. 2015;11:1519–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  217. Kosmides AK, Meyer RA, Hickey JW, et al. Biomimetic biodegradable artificial antigen presenting cells synergize with PD-1 blockade to treat melanoma. Biomaterials. 2017;118:16–26.

    CAS  PubMed  Google Scholar 

  218. Sakhtianchi R, Minchin RF, Lee KB, Alkilany AM, Serpooshan V, Mahmoudi M. Exocytosis of nanoparticles from cells: role in cellular retention and toxicity. Adv Colloid Interface Sci. 2013;201-202:18–29. https://doi.org/10.1016/jcis201310013.

    Article  CAS  PubMed  Google Scholar 

  219. Zaki NM, Nasti A, Tirelli N. Nanocarriers for cytoplasmic delivery: cellular uptake and intracellular fate of chitosan and hyaluronic acid-coated chitosan nanoparticles in a phagocytic cell model. Macromol Biosci. 2011;11:1747–60. https://doi.org/10.1002/mabi201100156.

    Article  CAS  PubMed  Google Scholar 

  220. Foged C, Brodin B, Frokjaer S, Sundblad A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm. 2005;298:315–22. https://doi.org/10.1016/jijpharm200503035.

    Article  CAS  PubMed  Google Scholar 

  221. Mottram PL, Leong D, Crimeen-Irwin B, et al. Type 1 and 2 immunity following vaccination is influenced by NP size: formulation of a model vaccine for respiratory syncytial virus. Mol Pharm. 2007;4:73–84. https://doi.org/10.1021/mp060096p.

    Article  CAS  PubMed  Google Scholar 

  222. Rice-Ficht AC, Arenas-Gamboa AM, Kahl-McDonagh MM, Ficht TA. Polymeric particles in vaccine delivery. Curr Opin Microbiol. 2010;13:106–12. https://doi.org/10.1016/jmib200912001.

    Article  CAS  PubMed  Google Scholar 

  223. Gratton SE, Ropp PA, Pohlhaus PD, et al. The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U S A. 2008;105:11613–8. https://doi.org/10.1073/pnas0801763105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  224. Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann MF. NPs target distinct dendritic cell populations according to their size. Eur J Immunol. 2008;38:1404–13. https://doi.org/10.1002/eji200737984.

    Article  CAS  PubMed  Google Scholar 

  225. Kourtis IC, Hirosue S, de Titta A, et al. Peripherally administered NPs target monocytic myeloid cells, secondary lymphoid organs and tumors in mice. PLoS One. 2013;8:e61646. https://doi.org/10.1371/journalpone0061646.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Singh D, McMillan JM, Liu XM, et al. Formulation design facilitates magnetic NP delivery to diseased cells and tissues. Nanomedicine (London). 2014;9:469–85. https://doi.org/10.2217/nnm.14.4.

    Article  CAS  Google Scholar 

  227. Jahan ST, Sadat SMA, Walliser M, Haddadi A. Targeted therapeutic nps: an immense promise to fight against cancer. J Drug Deliv 2017; 9090325. https://doi.org/10.1155/2017/9090325.

  228. Sperling RA, Parak WJ. Surface modification, functionalization and bioconjugation of colloidal inorganic NPs. Philos Trans A Math Phys Eng Sci. 2010;368:1333–83. https://doi.org/10.1098/rsta20090273.

    Article  CAS  PubMed  Google Scholar 

  229. Mohanan D, Slutter B, Henriksen-Lacey M, et al. Administration routes affect the quality of immune responses: a cross-sectional evaluation of particulate antigen-delivery systems. J Control Release. 2010;147:342–9. https://doi.org/10.1016/jjconrel201008012.

    Article  CAS  PubMed  Google Scholar 

  230. Maji M, Mazumder S, Bhattacharya S, et al. A lipid based antigen delivery system efficiently facilitates mhc class-i antigen presentation in dendritic cells to stimulate CD8(+) T-cells. Sci Rep. 2016;6:27206. https://doi.org/10.1038/srep27206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Chandrasekaran S, McGuire MJ, King MR. Sweeping lymph node micrometastases off their feet: an engineered model to evaluate natural killer cell mediated therapeutic intervention of circulating TCs that disseminate to the lymph nodes. Lab Chip. 2014;14:118–27. https://doi.org/10.1039/c3lc50584g.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors are thankful to the Department of Science & Technology (DST) Government of India, New Delhi, and Indian Council of Medical Research (ICMR) Government of India, New Delhi, for providing necessary financial support.

Author information

Authors and Affiliations

  1. Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Kamla Nehru Hospital,, Building (Gandhi Medical College Campus), Bhopal, Madhya Pradesh, 462001, India

    Arpit Bhargava, Rajnarayan Tiwari & Pradyumna Kumar Mishra

  2. Indore Institute of Pharmacy, Indore, India

    Dinesh Kumar Mishra

  3. School of Life Sciences, University of Rajasthan, Jaipur, India

    Nirmal Kumar Lohiya

  4. Department of General and Inorganic Chemistry, Saratov State University, Saratov, Russian Federation

    Irina Yu Goryacheva

Authors
  1. Arpit Bhargava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dinesh Kumar Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rajnarayan Tiwari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nirmal Kumar Lohiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Irina Yu Goryacheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pradyumna Kumar Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pradyumna Kumar Mishra.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhargava, A., Mishra, D.K., Tiwari, R. et al. Immune cell engineering: opportunities in lung cancer therapeutics. Drug Deliv. and Transl. Res. 10, 1203–1227 (2020). https://doi.org/10.1007/s13346-020-00719-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-020-00719-2

Keywords

Search

Navigation