Redox-Responsive Polyphosphate Nanosized Assemblies: A Smart Drug Delivery Platform for Cancer Therapy

• Published in: Biomacromolecules 2011-06, Vol.12 (6), p.2407-2415
• Main Authors: Liu, Jinyao, Pang, Yan, Huang, Wei, Zhu, Zhaoyang, Zhu, Xinyuan, Zhou, Yongfeng, Yan, Deyue
• Format: Article
• Language: English
• Subjects: Animals; Antimetabolites - metabolism; Antimetabolites - pharmacology; Buthionine Sulfoximine - metabolism; Buthionine Sulfoximine - pharmacology; Cell Survival - drug effects; Doxorubicin - metabolism; Doxorubicin - pharmacology; Drug Carriers - chemical synthesis; Drug Carriers - metabolism; Drug Delivery Systems - methods; Female; Flow Cytometry; Glutathione - analogs & derivatives; Glutathione - metabolism; Glutathione - pharmacology; HeLa Cells; Humans; Magnetic Resonance Spectroscopy; Mice; Micelles; Nanoparticles - chemistry; NIH 3T3 Cells; Oxidation-Reduction; Polyphosphates - chemical synthesis; Polyphosphates - metabolism; Surface-Active Agents - chemical synthesis; Surface-Active Agents - metabolism; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - pathology
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm2005164

Novel redox-responsive polyphosphate nanosized assemblies based on amphiphilic hyperbranched multiarm copolyphosphates (HPHSEP-star-PEP x ) with backbone redox-responsive, good biocompatibility, and biodegradability simultaneously have been designed and prepared successfully. The hydrophobic core and hydrophilic multiarm of HPHSEP-star-PEP x are composed of hyperbranched and linear polyphosphates, respectively. Benefiting from the amphiphilicity, HPHSEP-star-PEP x 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-PEP x 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-PEP x 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.