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Exploiting Nanocarriers for Combination Cancer Therapy

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Intracellular Delivery III

Part of the book series: Fundamental Biomedical Technologies ((FBMT))

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Abstract

Combination chemotherapy has vastly improved patient outcomes following treatment for cancer. Combining multiple drugs with non-overlapping mechanisms of action has been shown to forestall the development of drug resistance, leading to increased efficacy. Emerging insights into cancer pathophysiology from tumor genomics, metabolomics, and proteomics now present us with unprecedented opportunities to combine targeted molecular therapies together, or to combine molecular therapies with cytotoxic chemotherapy in a rationally designed manner based on unique molecular signatures. However, the clinical implementation of these improved drug combinations is frequently limited by overlapping drug toxicities. By using new nanotechnology platforms to enhance tumor targeting, and provide precise spatial and temporal control of drug delivery for each agent within a multi-drug regimen, it should be possible to mitigate these toxicity limitations and treat tumors with increasing safety, efficacy and durability. This chapter discusses recent efforts in developing nanoparticles to deliver multiple types of drugs for temporally-sequenced concurrent or sequential combination chemotherapy.

*Authors contributed equally to this work.

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Abbreviations

17-AAG:

17-allylamino-17-demethoxygeldanamycin

5-FU:

5-fluorouracil

6MP:

6-mercaptopurine (6MP)

AlClPc:

aluminum chloride phthalocyanine

dsRNA:

double-stranded RNA

EGFR:

epidermal growth factor receptor

EPR:

enhanced permeability and retention

HMSNs:

hollow mesoporous silica nanoparticles

LbL:

Layer-by-Layer

miRNA:

microRNA

mRNA:

messenger RNA

MMs:

macromonomers

MOMP:

nitrogen mustard with vincristine, methotrexate, and prednisone

MOPP:

nitrogen mustard with vincristine, procarbazine, and prednisone

MPS:

mononuclear phagocyte system

MSNs:

mesoporous silica nanoparticles

MTD:

maximum-tolerated-dose

NSAIDSs:

nonsteroidal anti-inflammatory drugs

PCL:

poly caprolactone

PDT:

photodynamic therapy

PEG:

poly(ethylene glycol)

PGLA:

poly(d,l-lactide-co-glycolide)

PLA:

polylactic acid

RNAi:

RNA interference

siRNA:

small interfering RNA

SSRIs:

serotonin reuptake inhibitors

TNBC:

triple-negative breast cancer

UCNs:

upconversion nanoparticles

UV:

ultraviolet

VAMP:

vincristine, amethopterin, 6MP, and prednisone

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Acknowledgments

We wish to thank Dr Ian Cannell for reading and commenting on the chapter.

Financial Support

This work was supported by the Ovarian Cancer Research Foundation (MBY, PTH; Program Project Development Grant), the Breast Cancer Alliance (MBY, PTH; Exceptional Project Award), the Department of Defense (PTH; CDMRP Ovarian Cancer Research Program Teal Innovator Award), the National Institutes of Health (MBY; R01-ES015339, R01-GM104047, ECD; NIBIB 1F32EB017614-02), and the Misrock Foundation (YWK). Support was provided in part by the Koch Institute Support Grant (P30-CA14051) from the National Cancer Institute.

Conflict of Interest Statement

The authors declare no conflict of interest.

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    Authors and Affiliations

    1. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

      Yi Wen Kong, Erik C. Dreaden, Paula T. Hammond & Michael B. Yaffe

    2. Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

      Yi Wen Kong & Michael B. Yaffe

    3. Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

      Erik C. Dreaden & Paula T. Hammond

    4. Institute for Soldier Nanotechnologies, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

      Paula T. Hammond

    5. Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA

      Michael B. Yaffe

    6. Divisions of Acute Care Surgery, Trauma, and Critical Care and Surgical Oncology, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02115, USA

      Michael B. Yaffe

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    1. Yi Wen Kong
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    Correspondence to Paula T. Hammond or Michael B. Yaffe .

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    1. Biomolecular and Chemical Engineering, Vanderbilt University Biomolecular and Chemical Engineering, Nashville, Tennessee, USA

      Aleš Prokop

    2. Pharmaceutical Sciences, Midwestern University Pharmaceutical Sciences, GLENDALE, Arizona, USA

      Volkmar Weissig

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    Kong, Y.W., Dreaden, E.C., Hammond, P.T., Yaffe, M.B. (2016). Exploiting Nanocarriers for Combination Cancer Therapy. In: Prokop, A., Weissig, V. (eds) Intracellular Delivery III. Fundamental Biomedical Technologies. Springer, Cham. https://doi.org/10.1007/978-3-319-43525-1_16

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