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基于放射性核素I标记白蛋白与羧甲基纤维素静电自组装的pH敏感纳米凝胶用于癌症的协同联合化学-放射性同位素治疗。

pH-Sensitive nanogels based on the electrostatic self-assembly of radionuclide I labeled albumin and carboxymethyl cellulose for synergistic combined chemo-radioisotope therapy of cancer.

作者信息

Liu Kefeng, Zheng Dan, Zhao Jingyang, Tao Yinghua, Wang Yingsa, He Jing, Lei Jiandu, Xi Xingjun

机构信息

Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.

出版信息

J Mater Chem B. 2018 Aug 7;6(29):4738-4746. doi: 10.1039/c8tb01295d. Epub 2018 Jul 3.

Abstract

Development of biocompatible and biodegradable nanocarriers with multiple functionalities has attracted great interest in recent years. In this study, a hybrid hydrogel nanoparticle (nanogel) platform based on the self-assembly of carboxymethyl cellulose (CMC) and bovine serum albumin (BSA) is presented for the first time. It was facile to realize the efficient co-delivery of radionuclide I and chemotherapeutic drugs such as camptothecin (CPT) to achieve the combined chemo-radioisotope therapy of cancer. Notably, a nanogel was prepared by a simple and green electrostatic interaction approach, instead of chemical reaction, showing typical spherical shape with average size about 120 nm, high drug loading capacity, robust stability and low hemolysis. Interestingly, such nanogels exhibited pH-dependent drug release profile, leading to significant reduction of damage to normal tissues. Furthermore, the as-prepared nanogels could effectively promote intracellular uptake, prolong blood circulation time and enhance accumulation in the tumor tissues. As a result, an excellent therapeutic effect was achieved both in vitro and in vivo through combined chemo-radioisotope therapy. Collectively, this study presents the preparation of a novel green nanocarrier by a reliable and simple approach, and offers an effective strategy for the combination of chemotherapy and radiotherapy.

摘要

近年来,具有多种功能的生物相容性和可生物降解纳米载体的研发引起了极大关注。在本研究中,首次提出了一种基于羧甲基纤维素(CMC)和牛血清白蛋白(BSA)自组装的混合水凝胶纳米颗粒(纳米凝胶)平台。实现放射性核素碘与喜树碱(CPT)等化疗药物的高效共递送以实现癌症的联合化学-放射性同位素治疗变得轻而易举。值得注意的是,纳米凝胶是通过简单且绿色的静电相互作用方法而非化学反应制备的,呈现典型的球形,平均尺寸约为120 nm,具有高载药能力、强大的稳定性和低溶血率。有趣的是,此类纳米凝胶呈现pH依赖性药物释放曲线,从而显著减少对正常组织的损伤。此外,所制备的纳米凝胶可有效促进细胞内摄取、延长血液循环时间并增强在肿瘤组织中的蓄积。结果,通过联合化学-放射性同位素治疗在体外和体内均实现了优异的治疗效果。总体而言,本研究通过可靠且简单的方法展示了新型绿色纳米载体的制备,并为化疗和放疗的联合提供了有效策略。

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