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Redox-Responsive Polyphosphate Nanosized Assemblies: A Smart Drug Delivery Platform for Cancer Therapy
作者:Liu, J.Y.; Pang, Y.; Huang, W.*; Zhu, Z. Y.; Zhu, X. Y.; Zhou, Y. F.; Yan, D.Y.*
关键字:Redox-Responsive, Assemblies, Drug Delivery
论文来源:期刊
具体来源:Biomacromolecules 2011, 12, 2407. http://pubs.acs.org/doi/pdf/10.1021/bm2005164
发表时间:2011年

Abstract Image


Novel redox-responsive polyphosphate nanosized assemblies based on amphiphilic hyperbranched multiarm copolyphosphates (HPHSEP-star-PEPx) with backbone redox-responsive, good biocompatibility, and biodegradability simultaneously have been designed and prepared successfully. The hydrophobic core and hydrophilic multiarm of HPHSEP-star-PEPx are composed of hyperbranched and linear polyphosphates, respectively. Benefiting from the amphiphilicity, HPHSEP-star-PEPx can self-assemble into spherical micellar nanoparticles in aqueous media with tunable size from about 70 to 100 nm via adjusting the molecular weight of PEP multiarm. Moreover, HPHSEP-star-PEPx micellar structure can be destructed under reductive environment and result in a triggered drug release behavior. The glutathione-mediated intracellular drug delivery was investigated against a HeLa human cervical carcinoma cell line, and the results indicate that doxorubicin-loaded (DOX-loaded) HPHSEP-star-PEPx micelles show higher cellular proliferation inhibition against glutathione monoester pretreated HeLa cells than that of the nonpretreated ones. In contrast, the DOX-loaded micelles exhibit lower inhibition against buthionine sulfoximine pretreated HeLa cells. These results suggest that such redox-responsive polyphosphate micelles can rapidly deliver anticancer drugs into the nuclei of tumor cells enhancing the inhibition of cell proliferation and provide a favorable platform to construct excellent drug delivery systems for cancer therapy.