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角蛋白-单宁酸复合纳米颗粒作为 pH/GSH 双重响应的载药系统用于阿霉素。

Keratin-tannic acid complex nanoparticles as pH/GSH dual responsive drug carriers for doxorubicin.

机构信息

Jiangsu Key Laboratory of Bio-functional Materials, Department of Materials Science and Engineering, School of Chemistry and Materials Science, Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Nanjing Normal University, Nanjing, P.R. China.

出版信息

J Biomater Sci Polym Ed. 2021 Jun;32(9):1125-1139. doi: 10.1080/09205063.2021.1906074. Epub 2021 Apr 7.

Abstract

Drug-loaded nanoparticles have been widely used in the field of tumor treatment due to their low side effects and reduced frequency of administration. In this study, pH and glutathione (GSH) dual-responsive keratin-tannic acid (TA) complex nanoparticles were established to trigger drug release under tumor microenvironments. Reductive keratin was first extracted using a reduction method. Then, keratin-TA complex nanoparticles (KNPs) were self-assembled non-covalent interaction and further stabilized by self-crosslinking of thiols. This method was facile and green without chemicals during the whole procedure. KNPs exhibited pH and GSH dual responsiveness as well as charge reversibility in the simulated tumor microenvironment. The anticancer drug of doxorubicin (DOX) was loaded on KNPs by hydrophobicity and hydrogen bonds. Drug-loaded KNPs accelerated drug release under mimicked tumor microenvironments, performing high toxic against A549 cells while low toxic on normal cells. Besides, drug-loaded nanoparticles could be endocytosed by tumor cells. Based on these results, KNPs may serve as drug carriers for therapeutic delivery.

摘要

载药纳米颗粒由于其副作用低和给药频率降低,已广泛应用于肿瘤治疗领域。在这项研究中,建立了 pH 和谷胱甘肽 (GSH) 双重响应角蛋白-单宁酸 (TA) 复合纳米颗粒,以在肿瘤微环境下触发药物释放。首先采用还原法提取还原角蛋白。然后,通过巯基的自交联,非共价相互作用自组装角蛋白-TA 复合纳米颗粒 (KNPs)。该方法在整个过程中简便、绿色,无需使用化学物质。KNPs 在模拟肿瘤微环境中表现出 pH 和 GSH 双重响应性以及电荷反转性。阿霉素 (DOX) 抗癌药物通过疏水性和氢键加载到 KNPs 上。载药 KNPs 在模拟肿瘤微环境下加速药物释放,对 A549 细胞表现出高毒性,而对正常细胞毒性低。此外,载药纳米颗粒可以被肿瘤细胞内吞。基于这些结果,KNPs 可以作为治疗药物的载体。

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