Platinum covalent shell cross-linked micelles designed to deliver doxorubicin for synergistic combination cancer therapy
Caiying Zhu,1,* Jingjing Xiao,1,* Ming Tang,2 Hua Feng,1 Wulian Chen,3 Ming Du1 1Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital, Shanghai Medical College, Fudan University, Shanghai, 2Department of Otorhinolaryngology-Head and Neck Surgery, Ningb...
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| Formato: | article |
| Lenguaje: | EN |
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Dove Medical Press
2017
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/fe464a9442bb438aba7609ee564c515e |
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| Sumario: | Caiying Zhu,1,* Jingjing Xiao,1,* Ming Tang,2 Hua Feng,1 Wulian Chen,3 Ming Du1 1Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital, Shanghai Medical College, Fudan University, Shanghai, 2Department of Otorhinolaryngology-Head and Neck Surgery, Ningbo Medical Center, Li Huli Hospital, Ningbo, 3State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, China *These authors contributed equally to this work Abstract: The preparation of polymer therapeutics capable of controlled release of multiple chemotherapeutic drugs has remained a tough problem in synergistic combination cancer therapy. Herein, a novel dual-drug co-delivery system carrying doxorubicin (DOX) and platinum(IV) (Pt[IV]) was developed. An amphiphilic diblock copolymer, PCL-b-P(OEGMA-co-AzPMA), was synthesized and used as a nanoscale drug carrier in which DOX and Pt(IV) could be packaged together. The copolymers were shell cross-linked by Pt(IV) prodrug via a click reaction. Studies on the in vitro drug release and cellular uptake of the dual-drug co-delivery system showed that the micelles were effectively taken up by the cells and simultaneously released drugs in the cells. Futhermore, the co-delivery polymer nanoparticles caused much higher cell death in HeLa and A357 tumor cells than either the free drugs or single-drug-loaded micelles at the same dosage, exhibiting a synergistic combination of DOX and Pt(IV). The results obtained with the shell cross-linked micelles based on an anticancer drug used as a cross-linking linkage suggested a promising application of the micelles for multidrug delivery in combination cancer therapy. Keywords: dual-drug co-delivery system, amphiphilic diblock copolymer, shell cross-linked micelles, synergistic combination cancer therapy |
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