Abstract

The development of resistance to variety of chemotherapeutic agents is one of the major challenges in effective cancer treatment. Tumor cells are able to generate a multi-drug resistance (MDR) phenotype due to microenvironmental selection pressures. This review addresses the use of nanotechnology-based delivery systems to overcome MDR in solid tumors. Our own work along with evidence from the literature illustrates the development of various types of engineered nanocarriers specifically designed to enhance tumor-targeted delivery through passive and active targeting strategies. Additionally, multi-functional nanocarriers are developed to enhance drug delivery and overcome MDR by either simultaneous or sequential delivery of resistance modulators (e.g., with P-glycoprotein substrates), agents that regulate intracellular pH, agents that lower the apoptotic threshold (e.g., with ceramide), or in combination with energy delivery (e.g., sound, heat, and light) to enhance the effectiveness of anticancer agents in refractory tumors. In preclinical studies, the use of multi-functional nanocarriers has shown significant promise in enhancing cancer therapy, especially against MDR tumors.

Notes

Author's accepted manuscript version of article published in Cancer Treatment Reviews 34(7), November 2008: 592–602. doi:10.1016/j.ctrv.2008.04.003.

Keywords

multi-drug resistance (MDR), multi-functional nanocarriers, drug delivery, resistance modulators, energy delivery

Subject Categories

Nanomedicine, Drug resistance in cancer cells, Multidrug resistance

Disciplines

Oncology | Pharmaceutics and Drug Design

Publisher

Elsevier Ltd.

Publication Date

11-2008

Rights Information

Copyright 2008

Rights Holder

Elsevier Ltd

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