Zinc finger-inspired nanohydrogels with glutathione/pH triggered degradation based on coordination substitution for highly efficient delivery of anti-cancer drugs

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• 作者：Zihao Zhang ; Jiaxun Wan ; Luyan Sun ; Yongjing Li ; Jia Guo ; Changchun Wang ; ^{ccwang@fudan.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Zinc(II)-crosslinked nanohydrogels ; Folate-PEG conjugation ; Glutathione/pH triggered degradation ; Coordination substitution ; Targeted drug delivery
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 March 2016
• 年：2016
• 卷：225
• 期：Complete
• 页码：96-108
• 全文大小：2412 K

文摘

Biodegradable materials used for drug delivery are of great demand due to their ability to degrade into low molecular weight species and further excrete from the body by metabolism. Herein, we report a new kind of zinc(II) crosslinked poly(methacrylic acid) nanohydrogels (ZCLNs) inspired by zinc finger proteins with dual stimuli-triggered degradation (glutathione and pH) for the first time. Compared with the disulfide bond crosslinked nanohydrogels, this new kind of ZCLNs is beneficial to the degradation of a wide range of cells, including normal cells. Ex vivo fluorescence images showed that the DOX-loaded folate-PEG conjugated zinc(II)-crosslinked polymeric nanohydrogels (FPZCLNs-15) preferentially accumulated in tumor tissue and the accumulation in normal tissues was much less compared with DOX-loaded PZCLNs-15 (non-targeted nanohydrogels) and free DOX, the FPZCLNs-15 (targeting system) delivered DOX to the tumor site with approximately 3.6- and 1.6-fold higher than free DOX and PZCLNs-15, respectively. Meanwhile, the PZCLNs-15 and FPZCLNs-15 reduced the concentration of DOX in the heart by 3.2- and 5.0-fold respectively, as compared to the free DOX. Moreover, a superior tumor growth inhibition and negligible damage to normal organs like the heart and kidney, which is reported to be vulnerable to DOX-associated side effects, are further demonstrated.