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Injectable Thermosensitive Polypeptide-Based CDDP-Complexed Hydrogel for Improving Localized Antitumor Efficacy
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-11-27 00:00:00 , DOI: 10.1021/acs.biomac.7b01374 Shuangjiang Yu 1, 2 , Dianliang Zhang 1, 3 , Chaoliang He 1 , Wujin Sun 2 , Rangjuan Cao 4 , Shusen Cui 4 , Mingxiao Deng 3 , Zhen Gu 2 , Xuesi Chen 1
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-11-27 00:00:00 , DOI: 10.1021/acs.biomac.7b01374 Shuangjiang Yu 1, 2 , Dianliang Zhang 1, 3 , Chaoliang He 1 , Wujin Sun 2 , Rangjuan Cao 4 , Shusen Cui 4 , Mingxiao Deng 3 , Zhen Gu 2 , Xuesi Chen 1
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In this study, a type of novel thermosensitive polypeptide-based hydrogel with tunable gelation behavior through changing the content of carboxyl groups was developed for the purpose of improving the cisplatin (CDDP) release behavior and enhancing the localized antitumor efficiency. The introduction of carboxyl groups in methoxy-poly(ethylene glycol)-b-(poly(γ-ethyl-l-glutamate-co-l-glutamic acid) (mPEG-b-P(ELG-co-LG)) not only led to adjustable mechanical properties of the hydrogel but also significantly reduced the burst release of the drug through the complexation between the carboxyl groups of polypeptide and CDDP. Furthermore, both the good biocompatibility and the biodegradable properties of mPEG-b-P(ELG-co-LG) hydrogel were observed in vivo. Interestingly, the CDDP-complexed mPEG-b-P(ELG-co-LG) hydrogel exhibited significantly enhanced antitumor efficacy in vivo compared to the mPEG-b-PELG hydrogel loaded with CDDP without complexation, although a lower cytotoxicity and IC50 of the CDDP-complexed hydrogel was observed in vitro. Overall, the new type of injectable CDDP-complexed hydrogel may serve as an efficient platform for sustained CDDP delivery in localized tumor therapy.
中文翻译：
注射型热敏多肽基CDDP复合水凝胶，可提高局部抗肿瘤功效
在这项研究中，一种新型的基于热敏多肽的水凝胶通过改变羧基含量具有可调节的胶凝行为，目的是改善顺铂（CDDP）的释放行为并提高局部抗肿瘤效率。-在甲氧基聚（乙二醇）的引进羧基b - （聚（γ-乙基升-glutamate-共-升-谷氨酸）（的mPEG- b -P（ELG-共-LG））不仅导致水凝胶的可调节机械性能，而且通过多肽和CDDP羧基之间的络合显着减少了药物的爆发释放。此外，在体内观察到mPEG- b- P（ELG- co- LG ）水凝胶的良好的生物相容性和可生物降解的性质。有趣的是，与载有CDDP的mPEG- b -PELG水凝胶相比，CDDP复合的mPEG- b -P（ELG- co -LG）水凝胶在体内显示出显着增强的抗肿瘤功效，尽管细胞毒性和IC 50较低在体外观察到CDDP复合水凝胶的“溶解”。总体而言，新型可注射CDDP复合水凝胶可作为局部肿瘤治疗中CDDP持续递送的有效平台。
更新日期：2017-11-28
中文翻译：
注射型热敏多肽基CDDP复合水凝胶，可提高局部抗肿瘤功效
在这项研究中，一种新型的基于热敏多肽的水凝胶通过改变羧基含量具有可调节的胶凝行为，目的是改善顺铂（CDDP）的释放行为并提高局部抗肿瘤效率。-在甲氧基聚（乙二醇）的引进羧基b - （聚（γ-乙基升-glutamate-共-升-谷氨酸）（的mPEG- b -P（ELG-共-LG））不仅导致水凝胶的可调节机械性能，而且通过多肽和CDDP羧基之间的络合显着减少了药物的爆发释放。此外，在体内观察到mPEG- b- P（ELG- co- LG ）水凝胶的良好的生物相容性和可生物降解的性质。有趣的是，与载有CDDP的mPEG- b -PELG水凝胶相比，CDDP复合的mPEG- b -P（ELG- co -LG）水凝胶在体内显示出显着增强的抗肿瘤功效，尽管细胞毒性和IC 50较低在体外观察到CDDP复合水凝胶的“溶解”。总体而言，新型可注射CDDP复合水凝胶可作为局部肿瘤治疗中CDDP持续递送的有效平台。
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