Zhou Ke, Zhu Yixin, Chen Xuling, Li Lingbing, Xu Wei
Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province 250012, China.
Mater Sci Eng C Mater Biol Appl. 2020 Sep;114:111006. doi: 10.1016/j.msec.2020.111006. Epub 2020 May 5.
Tumor-responsive nanocarriers are highly valuable and demanded for smart anticancer drug delivery, where a quick release of chemotherapeutic drugs in tumors is preferred. Herein, a redox and MMP-2 sensitive nanoparticle has been designed for targeted delivery of PTX. Bovine serum albumin as a targeting ligand and gelatin as a hydrophilic carrier and MMP-2 sensitive reagent were used to construct the nanoparticles. Disulfide containing prodrug (PTX-SS-COOH) was grafted to the sulfhydryl modified gelatin to form the redox sensitive amphiphilic polymer. The nanoparticles were formed by self-assembly of amphiphilic polymer and BSA covering. Furthermore the modified sulfhydryl group on the gelatin can form a disulfide bond by self-crosslinking in the air, which endows the nanoparticle with a stable structure. The nanoparticle was sensitive to changes in MMP-2 concentration and redox potential, resulting in multiple responsive drug delivery to the tumor microenvironment. We further verified the anticancer effect of the nanoparticles both in vitro and in vivo, the nanoparticle (BSA/Gel-SS-PTX/PTX-SS-COOH NPs) demonstrated an excellent anticancer efficiency.
肿瘤响应性纳米载体对于智能抗癌药物递送具有很高的价值且需求很大，其中在肿瘤中快速释放化疗药物是首选。在此，设计了一种对氧化还原和基质金属蛋白酶-2（MMP-2）敏感的纳米颗粒用于紫杉醇（PTX）的靶向递送。使用牛血清白蛋白作为靶向配体，明胶作为亲水载体和MMP-2敏感试剂来构建纳米颗粒。将含二硫键的前药（PTX-SS-COOH）接枝到巯基修饰的明胶上，形成氧化还原敏感的两亲性聚合物。纳米颗粒通过两亲性聚合物的自组装和牛血清白蛋白覆盖形成。此外，明胶上修饰的巯基可在空气中通过自交联形成二硫键，这赋予纳米颗粒稳定的结构。该纳米颗粒对MMP-2浓度和氧化还原电位的变化敏感，从而实现向肿瘤微环境的多重响应性药物递送。我们进一步在体外和体内验证了纳米颗粒的抗癌效果，该纳米颗粒（牛血清白蛋白/明胶-SS-紫杉醇/PTX-SS-COOH纳米颗粒）表现出优异的抗癌效率。
