title: Redox-responsive polyphosphate nanosized assemblies: a smart drug delivery platform for cancer therapy.
abstract: 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.
authors.affiliation: School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
authors.forename: Jinyao
authors.initials: J
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Pang
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Deyue
authors.initials: D
authors.lastname: Yan
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000378:metabolism / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000378:metabolism / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005434:Flow Cytometry; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry; D010084:Oxidation-Reduction; D011122:Polyphosphates / Q000138:chemical synthesis* / Q000378:metabolism; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000963:Antimetabolites; D004337:Drug Carriers; D008823:Micelles; D011122:Polyphosphates; D013501:Surface-Active Agents; D019328:Buthionine Sulfoximine; C042431:S-ethyl glutathione; D004317:Doxorubicin; D005978:Glutathione