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Poly(l-lactide)-Vitamin E TPGS Nanoparticles Enhanced the Cytotoxicity of Doxorubicin in Drug-Resistant MCF-7 Breast Cancer Cells

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    Poly(l-lactide)-Vitamin E TPGS Nanoparticles Enhanced the Cytotoxicity of Doxorubicin in Drug-Resistant MCF-7 Breast Cancer Cells
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    Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
    * To whom correspondence should be addressed. Tel.: +886-4-22840411, ext. 428. Fax: +886-4-22862547. E-mail: [email protected]
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    Biomacromolecules

    Cite this: Biomacromolecules 2010, 11, 10, 2576–2582
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    https://doi.org/10.1021/bm1005195
    Published August 19, 2010
    Copyright © 2010 American Chemical Society
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    Multiple drug resistance (MDR) seriously reduces the efficacy of many chemotherapeutic agents for cancer. P-Glycoprotein, an efflux pump overexpressed on the cell surface, plays an important role in drug resistance, but several surfactants, such as vitamin E TPGS, can inhibit P-glycoprotein. In this study, a polylactide-surfactant block copolymer poly(l-lactide)-vitamin E TPGS (PLA-TPGS) was synthesized using bidentate sulfonamide zinc ethyl complex as an efficient catalyst, and its self-assembled nanoparticles were used as carriers of doxorubicin. We first found that the activity of P-glycoprotein in drug-resistant breast cancer MCF-7/ADR cells was decreased after incubation with PLA-TPGS nanoparticles. In addition, the nuclear accumulation and cytotoxicity of doxorubicin were significantly increased by encapsulation into the nanoparticles. The enhanced efficacy of the doxorubicin-loaded PLA-TPGS nanoparticles may result from the combination of inhibition of efflux and increased entry of doxorubicin into the nucleus in drug-resistant MCF-7/ADR cells. Therefore, this innovative delivery system has potential to act as a nanomedicine for therapy of both drug-sensitive and drug-resistant cancer.

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    Synthetic procedure and structure of Zn-complex catalyst, 1H NMR for PLA-TPGS copolymer, stability of nanoparticles, P-gp expression, and intracellular distribution of doxorubicin for polymer-treated cells. This material is available free of charge via the Internet at http://pubs.acs.org.

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    Cite this: Biomacromolecules 2010, 11, 10, 2576–2582
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    https://doi.org/10.1021/bm1005195
    Published August 19, 2010
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