Hydrogen Sulfide Triggered Charge-Reversal Micelles for Cancer-Targeted Drug Delivery and Imaging

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• 作者：Haitao Zhang ; Xiuqi Kong ; Yonghe Tang ; Weiying Lin
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：June 29, 2016
• 年：2016
• 卷：8
• 期：25
• 页码：16227-16239
• 全文大小：838K
• 年卷期：0
• ISSN：1944-8252

文摘

Currently, the development of polymeric micelles combining diagnosis and targeted therapy is theoretically and practically significant in cancer treatment. In addition, it has been reported that cancer cells can produce large amounts of hydrogen sulfide (H₂S) and their survival depends on the content of H₂S. In this study, a series of N-(2-hydroxyethyl)-4-azide-1,8-naphthalimide ended amphiphilic diblock copolymer poly(2-hydroxyethyl methacrylate)-block-poly(methyl methacrylate) (N₃-Nap-PHEMA-b-PMMA-N₃) micelles were prepared. Around cancer tissues, the N₃-Nap-PHEMA₄₅-b-PMMA₄₂-N₃ micelles exhibited dual characteristics of monitoring H₂S and H₂S triggered charge reversal with the reduction of the azido group. The surface charge of N₃-Nap-PHEMA₄₅-b-PMMA₄₂-N₃ micelles reversed from negative to positive after monitoring H₂S. With H₂S triggered charge reversal, the cellular uptake of DOX-loaded N₃-Nap-PHEMA₄₅-b-PMMA₄₂-N₃ micelles was effectively enhanced through electrostatic attraction mediated targeting, and a fast doxorubicin (DOX) release rate was observed. The MTT assay demonstrated that N₃-Nap-PHEMA₄₅-b-PMMA₄₂-N₃ micelles were biocompatible to HeLa cells, and DOX-loaded N₃-Nap-PHEMA₄₅-b-PMMA₄₂-N₃ micelles showed enhanced cytotoxicity in HeLa cells in the presence of H₂S. Furthermore, in vivo fluorescence imaging and biodistribution experiments revealed that DOX-loaded N₃-Nap-PHEMA₄₅-b-PMMA₄₂-N₃ micelles could provide good tumor imaging and accumulate in tumor tissue. Therefore, N₃-Nap-PHEMA₄₅-b-PMMA₄₂-N₃ micelles can be used as a promising platform for tumor diagnosis and therapy.