Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 65, Issue 13-14, Pages 1731-1747Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2013.09.001
Keywords
Nanoparticles; Efflux transporters; Excipients; Endocytosis; Efflux inhibitors; Tumor penetration; Interstitial fluid pressure; Extracellular matrix; Transport barriers
Categories
Funding
- NIH [CA116641, CA093453]
- CDMRP [545593, CA093453] Funding Source: Federal RePORTER
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Tumor cells develop resistance to chemotherapeutic drugs through multiple mechanisms. Overexpression of efflux transporters is an important source of drug resistance. Efflux transporters such as P-glycoprotein reduce intracellular drug accumulation and compromise drug efficacy. Various nanoparticle-based approaches have been investigated to overcome efflux-mediated resistance. These include the use of formulation excipients that inhibit transporter activity and co-delivery of the anticancer drug with a specific inhibitor of transporter function or expression. However, the effectiveness of nanoparticles can be diminished by poor transport in the tumor tissue. Hence, adjunct therapies that improve the intratumoral distribution of nanoparticles may be vital to the successful application of nanotechnology to overcome tumor drug resistance. This review discusses the mechanisms of tumor drug resistance and highlights the opportunities and challenges in the use of nanoparticles to improve the efficacy of anticancer drugs against resistant tumors. (C) 2013 Elsevier B.V. All rights reserved.
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