Dendron-polymer hybrid mediated anticancer drug delivery for suppression of mammary cancer
来源期刊：JOURNAL OF MATERIALS SCIENCE TECHNOLOG2021年第4期
论文作者：Dayi Pan Xiuli Zheng Miao Chen Qianfeng Zhang Zhiqian Li Zhenyu Duan Qiyong Gong Zhongwei Gu Kui Luo
摘 要：Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity. Here we report a dendronized polymer-doxorubicin（DOX） hybrid（DPDH） with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate（LPDC）. The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4. DPDH efficiently enters 4 T1 cells and releases DOX to induce cytotoxicity and apoptosis. Owing to the dendronzied structure, DPDH has a significantly longer blood circulation time than LPDC. DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4 T1 mammary cancer model than LPDC as well as free drug, evidenced from tumor growth inhibition, TUNEL assessment and histological analysis. Biosafety of DPDH is also confirmed from hemolysis, body weight shifts during treatment and pathological analysis. This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.
Dayi Pan1，Xiuli Zheng1，Miao Chen2，Qianfeng Zhang1，Zhiqian Li1，Zhenyu Duan1，Qiyong Gong1，Zhongwei Gu1，Kui Luo1
1. Huaxi MR Research Center (HMRRC) , Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University2. Department of Orthodontics, West China Hospital of Stomatology, Sichuan University
摘 要：Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity. Here we report a dendronized polymer-doxorubicin（DOX） hybrid（DPDH） with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate（LPDC）. The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4. DPDH efficiently enters 4 T1 cells and releases DOX to induce cytotoxicity and apoptosis. Owing to the dendronzied structure, DPDH has a significantly longer blood circulation time than LPDC. DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4 T1 mammary cancer model than LPDC as well as free drug, evidenced from tumor growth inhibition, TUNEL assessment and histological analysis. Biosafety of DPDH is also confirmed from hemolysis, body weight shifts during treatment and pathological analysis. This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.
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