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Design and Synthesis of Dual-Responsive Carbon Nanodots Loaded with Cisplatin for Targeted Therapy of Lung Cancer Therapy and Nursing Care

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Abstract

The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivity, and inability of the drug to cross cellular barriers. To overcome these limitations, various types of drug delivery systems have been explored, and recently, carbon dots (CDs) materials have also garnered attention in the field of drug delivery. In this study, we describe the preparation, characterization, and in vitro testing of the PEGlyated carbon dots (CDs) loaded with cisplatin (CDDP) termed as (CDs@CDDP). Further, the CDs@CDDP decorated with PEGylated iRGD peptide (named as CDs@CDDP-iRGD. The electroscopic and spectroscopic methods are verified by the CDs@CDDP-iRGD. Two lung cancers (A549 and HEL-299) and a non-cancerous cell line (HUVEC) were examined for the cytotoxicity of nanoparticles in vitro. The nanoparticles effectively destroy cancer cells without damaging the non-cancerous cell lines. Also, the dual AO-EB fluorescent staining assay identified programmed cell death by morphological changes in the cells. The findings of our investigations also attest to promising reach and potency treatment and nursing care management of CDs@CDDP-iRGD nanoparticles for specific cancer therapy beyond platinum medicines.

Graphic Abstract

We have efficiently engineered the PEGlyated carbon dots loaded with cisplatin decorated with PEGylated iRGD peptide. The nanoparticles were confirmed by the various spectral methods (IR, UV, DLS and HR-TEM techiniques). Further, we screened the CDDP, CDs@CDDP and CDs@CDDP-iRGD, for human lung cancer cells. Additionally, CDDP, CDs@CDDP and CDs@CDDP-iRGD NPs effectively induce apoptosis in human lung cancer cells and the morphological changes were monitored through the AO-EB staining, and nuclear (Hoechst 33452) staining methods.

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References

  1. S. Khan, N. C. Verma, S. Chethana, and C. K. Nandi (2018). Carbon dots for single-molecule imaging of the nucleolus. ACS Appl. Nano Mater. 1, 483–487. https://doi.org/10.1021/acsanm.7b00175.

    Article  CAS  Google Scholar 

  2. T.-Y. Wang, C.-Y. Chen, C.-M. Wang, Y. Z. Tan, and W.-S. Liao (2017). Multicolor functional carbon dots via one-step refluxing synthesis. ACS Sens. 2, 354–363. https://doi.org/10.1021/acssensors.6b00607.

    Article  CAS  PubMed  Google Scholar 

  3. L. Xiao and H. Sun (2018). Novel properties and applications of carbon nanodots. Nanoscale Horiz. 3, 565–597. https://doi.org/10.1039/C8NH00106E.

    Article  CAS  PubMed  Google Scholar 

  4. P. G. Luo, F. Yang, S.-T. Yang, S. K. Sonkar, L. Yang, J. J. Broglie, Y. Liu, and Y.-P. Sun (2014). Carbon-based quantum dots for fluorescence imaging of cells and tissues. RSC Adv. 4, 10791–10807. https://doi.org/10.1039/C3RA47683A.

    Article  CAS  Google Scholar 

  5. G. E. LeCroy, S. K. Sonkar, F. Yang, L. M. Veca, P. Wang, K. N. Tackett, J.-J. Yu, E. Vasile, H. Qian, Y. Liu, P. Luo, and Y.-P. Sun (2014). Toward structurally defined carbon dots as ultracompact fluorescent probes. ACS Nano 8, 4522–4529. https://doi.org/10.1021/nn406628s.

    Article  CAS  PubMed  Google Scholar 

  6. S. Li, Z. Guo, Y. Zhang, W. Xue, and Z. Liu (2015). Blood compatibility evaluations of fluorescent carbon dots. ACS Appl. Mater. Interfaces. 7, 19153–19162. https://doi.org/10.1021/acsami.5b04866.

    Article  CAS  PubMed  Google Scholar 

  7. S.-T. Yang, L. Cao, P. G. Luo, F. Lu, X. Wang, H. Wang, M. J. Meziani, Y. Liu, G. Qi, and Y.-P. Sun (2009). Carbon dots for optical imaging in Vivo. J. Am. Chem. Soc. 131, 11308–11309. https://doi.org/10.1021/ja904843x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Y.-Y. Yao, G. Gedda, W. M. Girma, C.-L. Yen, Y.-C. Ling, and J.-Y. Chang (2017). Magnetofluorescent carbon dots derived from crab shell for targeted dual-modality bioimaging and drug delivery. ACS Appl. Mater. Interfaces. 9, 13887–13899. https://doi.org/10.1021/acsami.7b01599.

    Article  CAS  PubMed  Google Scholar 

  9. T. Feng, X. Ai, G. An, P. Yang, and Y. Zhao (2016). Charge-convertible carbon dots for imaging-guided drug delivery with enhanced in vivo cancer therapeutic efficiency. ACS Nano 10, 4410–4420. https://doi.org/10.1021/acsnano.6b00043.

    Article  CAS  PubMed  Google Scholar 

  10. K. D. Patel, R. K. Singh, and H.-W. Kim (2019). Carbon-based nanomaterials as an emerging platform for theranostics. Mater. Horiz. 6, 434–469. https://doi.org/10.1039/C8MH00966J.

    Article  CAS  Google Scholar 

  11. T. Feng, X. Ai, H. Ong, and Y. Zhao (2016). Dual-responsive carbon dots for tumor extracellular microenvironment triggered targeting and enhanced anticancer drug delivery. ACS Appl. Mater. Interfaces 8, 18732–18740. https://doi.org/10.1021/acsami.6b06695.

    Article  CAS  PubMed  Google Scholar 

  12. V. Biju (2014). Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem. Soc. Rev. 43, 744–764. https://doi.org/10.1039/C3CS60273G.

    Article  CAS  PubMed  Google Scholar 

  13. W. Li, Q. Liu, P. Zhang, and L. Liu (2016). Zwitterionic nanogels crosslinked by fluorescent carbon dots for targeted drug delivery and simultaneous bioimaging. Acta Biomater. 40, 254–262. https://doi.org/10.1016/j.actbio.2016.04.006.

    Article  CAS  PubMed  Google Scholar 

  14. W. Liu, C. Li, Y. Ren, X. Sun, W. Pan, Y. Li, J. Wang, and W. Wang (2016). Carbon dots: surface engineering and applications. J. Mater. Chem. B 4, 5772–5788. https://doi.org/10.1039/C6TB00976J.

    Article  CAS  PubMed  Google Scholar 

  15. S. D. Hettiarachchi, R. M. Graham, K. J. Mintz, Y. Zhou, S. Vanni, Z. Peng, and R. M. Leblanc (2019). Triple conjugated carbon dots as a nano-drug delivery model for glioblastoma brain tumors. Nanoscale 11, 6192–6205. https://doi.org/10.1039/C8NR08970A.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. T. Feng, X. Ai, G. An, P. Yang, and Y. Zhao (2016). Correction to charge-convertible carbon dots for imaging-guided drug delivery with enhanced in vivo cancer therapeutic efficiency. ACS Nano 10, 5587. https://doi.org/10.1021/acsnano.6b02794.

    Article  CAS  PubMed  Google Scholar 

  17. A. R. Chowdhuri, T. Singh, S. K. Ghosh, and S. K. Sahu (2016). carbon dots embedded magnetic nanoparticles @chitosan @metal organic framework as a nanoprobe for pH sensitive targeted anticancer drug delivery. ACS Appl. Mater. Interfaces 8, 16573–16583. https://doi.org/10.1021/acsami.6b03988.

    Article  CAS  PubMed  Google Scholar 

  18. J. Zhou, W. Deng, Y. Wang, X. Cao, J. Chen, Q. Wang, W. Xu, P. Du, Q. Yu, J. Chen, M. Spector, J. Yu, and X. Xu (2016). Cationic carbon quantum dots derived from alginate for gene delivery: one-step synthesis and cellular uptake. Acta Biomater. 42, 209–219. https://doi.org/10.1016/j.actbio.2016.06.021.

    Article  CAS  PubMed  Google Scholar 

  19. S. Augustine, J. Singh, M. Srivastava, M. Sharma, A. Das, and B. D. Malhotra (2017). Recent advances in carbon based nanosystems for cancer theranostics. Biomater. Sci. 5, 901–952. https://doi.org/10.1039/C7BM00008A.

    Article  CAS  PubMed  Google Scholar 

  20. J. Ma, K. Kang, Y. Zhang, Q. Yi, and Z. Gu (2018). Detachable polyzwitterion-coated ternary nanoparticles based on peptide dendritic carbon dots for efficient drug delivery in cancer therapy. ACS Appl. Mater. Interfaces 10, 43923–43935. https://doi.org/10.1021/acsami.8b17041.

    Article  CAS  PubMed  Google Scholar 

  21. Z. A. I. Mazrad, K. Lee, A. Chae, I. In, H. Lee, and S. Y. Park (2018). Progress in internal/external stimuli responsive fluorescent carbon nanoparticles for theranostic and sensing applications. J. Mater. Chem. B 6, 1149–1178. https://doi.org/10.1039/C7TB03323K.

    Article  CAS  PubMed  Google Scholar 

  22. M. S. Kang, R. K. Singh, T.-H. Kim, J.-H. Kim, K. D. Patel, and H.-W. Kim (2017). Optical imaging and anticancer chemotherapy through carbon dot created hollow mesoporous silica nanoparticles. Acta Biomater. 55, 466–480. https://doi.org/10.1016/j.actbio.2017.03.054.

    Article  CAS  PubMed  Google Scholar 

  23. T. Sathiya Kamatchi, M. K. Mohamed Subarkhan, R. Ramesh, H. Wang, and J. G. Małecki (2020). Investigation into antiproliferative activity and apoptosis mechanism of new arene Ru(ii) carbazole-based hydrazone complexes. Dalton Trans. 49, 11385–11395. https://doi.org/10.1039/D0DT01476A.

    Article  CAS  PubMed  Google Scholar 

  24. S. Kasibhatla, G. P. Amarante-Mendes, D. Finucane, T. Brunner, E. Bossy-Wetzel, and D. R. Green (2006). Acridine orange/ethidium bromide (AO/EB) staining to detect apoptosis. CSH Protocols 2006, 799–803. https://doi.org/10.1101/pdb.prot4493.

    Article  Google Scholar 

  25. M. K. M. Subarkhan and R. Ramesh (2016). Ruthenium(II) arene complexes containing benzhydrazone ligands: synthesis, structure and antiproliferative activity. Inorg. Chem. Front. 3, 1245–1255. https://doi.org/10.1039/c6qi00197a.

    Article  CAS  Google Scholar 

  26. W.-Y. Zhang, Y.-J. Wang, F. Du, M. He, Y.-Y. Gu, L. Bai, L.-L. Yang, and Y.-J. Liu (2019). Evaluation of anticancer effect in vitro and in vivo of iridium(III) complexes on gastric carcinoma SGC-7901 cells. Eur. J. Med. Chem. 178, 401–416. https://doi.org/10.1016/j.ejmech.2019.06.003.

    Article  CAS  PubMed  Google Scholar 

  27. M. K. Mohamed Subarkhan, R. Ramesh, and Y. Liu (2016). Synthesis and molecular structure of arene ruthenium(ii) benzhydrazone complexes: impact of substitution at the chelating ligand and arene moiety on antiproliferative activity. New J Chem. 40, 9813–9823. https://doi.org/10.1039/C6NJ01936F.

    Article  CAS  Google Scholar 

  28. N. Mohan, M. K. Mohamed Subarkhan, and R. Ramesh (2018). Synthesis, antiproliferative activity and apoptosis-promoting effects of arene ruthenium(II) complexes with N, O chelating ligands. J Organomet Chem. https://doi.org/10.1016/j.jorganchem.2018.01.022.

    Article  Google Scholar 

  29. P. Tambe, P. Kumar, K. M. Paknikar, and V. Gajbhiye (2018). Decapeptide functionalized targeted mesoporous silica nanoparticles with doxorubicin exhibit enhanced apoptotic effect in breast and prostate cancer cells. Int. J. Nanomed. 13, 7669–7680. https://doi.org/10.2147/IJN.S184634.

    Article  CAS  Google Scholar 

  30. M. Pandurangan, G. Enkhtaivan, and D. H. Kim (2016). Anticancer studies of synthesized ZnO nanoparticles against human cervical carcinoma cells. J. Photochem. Photobiol. B Biol. 158, 206–211. https://doi.org/10.1016/j.jphotobiol.2016.03.002.

    Article  CAS  Google Scholar 

  31. M. K. Mohamed Subarkhan, L. Ren, B. Xie, C. Chen, Y. Wang, and H. Wang (2019). Novel tetranuclear ruthenium(II) arene complexes showing potent cytotoxic and antimetastatic activity as well as low toxicity in vivo. Eur J Med Chem. https://doi.org/10.1016/j.ejmech.2019.06.061.

    Article  PubMed  Google Scholar 

  32. N. Atale, S. Saxena, J. G. Nirmala, R. T. Narendhirakannan, S. Mohanty, and V. Rani (2017). Synthesis and characterization of sygyzium cumini nanoparticles for its protective potential in high glucose-induced cardiac stress: a green approach. Appl. Biochem. Biotechnol. 181, 1140–1154. https://doi.org/10.1007/s12010-016-2274-6.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Third Department of Respiratory Oncology, Harbin Medical University Cancer Hospital, Harbin, 150001, China

    Chunhe Zhou

  2. Department of Nursing, Harbin Medical University Cancer Hospital, Harbin, 150001, China

    Huiyan Li

  3. Medical Department, The Fourth Hospital of Harbin Medical University, Harbin, 150001, China

    Yi Liu

  4. Central Sterile Supply Department, The First Hospital Affiliated With Harbin Medical University, No.2075, 7th Avenue, Qunli District, Harbin, 150001, China

    Kun Wang

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  1. Chunhe Zhou
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  4. Kun Wang
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CZ and HL—Methodology, Resources, writing- Original draft preparation Writing- Reviewing and Editing; YL—Resources; KW—Supervision.

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Correspondence to Kun Wang.

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Zhou, C., Li, H., Liu, Y. et al. Design and Synthesis of Dual-Responsive Carbon Nanodots Loaded with Cisplatin for Targeted Therapy of Lung Cancer Therapy and Nursing Care. J Clust Sci 33, 331–338 (2022). https://doi.org/10.1007/s10876-020-01959-5

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  • DOI: https://doi.org/10.1007/s10876-020-01959-5

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