Huang He, Yang Da-Peng, Liu Minghuan, Wang Xiangsheng, Zhang Zhiyong, Zhou Guangdong, Liu Wei, Cao Yilin, Zhang Wen Jie, Wang Xiansong
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, National Tissue Engineering Center of China, Shanghai.
College of Chemical Engineering and Materials Science, Quanzhou Normal University, Quanzhou, People's Republic of China.
Int J Nanomedicine. 2017 Apr 6;12:2829-2843. doi: 10.2147/IJN.S128270. eCollection 2017.
Albumin-based nanoparticles (NPs) as a drug delivery system have attracted much attention owing to their nontoxicity, non-immunogenicity, great stability and ability to bind to many therapeutic drugs. Herein, bovine serum albumin (BSA) was utilized as a template to prepare Au-BSA core/shell NPs. The outer layer BSA was subsequently conjugated with -aconityl doxorubicin (DOX) and folic acid (FA) to create Au-BSA-DOX-FA nanocomposites. A list of characterizations was undertaken to identify the successful conjugation of drug molecules and targeted agents. In vitro cytotoxicity using a cell counting kit-8 (CCK-8) assay indicated that Au-BSA NPs did not display obvious cytotoxicity to MGC-803 and GES-1 cells in the concentration range of 0-100 μg/mL, which can therefore be used as a safe drug delivery carrier. Furthermore, compared with free DOX, Au-BSA-DOX-FA nanocomposites exhibited a pH-sensitive drug release ability and superior antitumor activity in a drug concentration-dependent manner. In vivo computed tomography (CT) imaging experiments showed that Au-BSA-DOX-FA nanocomposites could be used as an efficient and durable CT contrast agent for targeted CT imaging of the folate receptor (FR) overexpressed in cancer tissues. In vivo antitumor experiments demonstrated that Au-BSA-DOX-FA nanocomposites have selective antitumor activity effects on FR-overexpressing tumors and no adverse effects on normal tissues and organs. In conclusion, the Au-BSA-DOX-FA nanocomposite exhibits selective targeting activity, X-ray attenuation activity and pH-sensitive drug release activity. Therefore, it can enhance CT imaging and improve the targeting therapeutic efficacy of FR-overexpressing gastric cancers. Our findings suggest that Au-BSA-DOX-FA nanocomposite is a novel drug delivery carrier and a promising candidate for cancer theranostic applications.
基于白蛋白的纳米颗粒（NPs）作为一种药物递送系统，因其无毒、无免疫原性、稳定性高以及能够结合多种治疗药物的能力而备受关注。在此，牛血清白蛋白（BSA）被用作模板来制备金-牛血清白蛋白核/壳纳米颗粒。随后，外层的牛血清白蛋白与乌头酰阿霉素（DOX）和叶酸（FA）共轭，以制备金-牛血清白蛋白-DOX-FA纳米复合材料。进行了一系列表征以确定药物分子和靶向剂的成功共轭。使用细胞计数试剂盒-8（CCK-8）测定的体外细胞毒性表明，在0-100μg/mL的浓度范围内，金-牛血清白蛋白纳米颗粒对MGC-803和GES-1细胞没有明显的细胞毒性，因此可以用作安全的药物递送载体。此外，与游离DOX相比，金-牛血清白蛋白-DOX-FA纳米复合材料表现出pH敏感的药物释放能力，并以药物浓度依赖性方式具有优异的抗肿瘤活性。体内计算机断层扫描（CT）成像实验表明，金-牛血清白蛋白-DOX-FA纳米复合材料可以用作高效持久的CT造影剂，用于对癌组织中过表达的叶酸受体（FR）进行靶向CT成像。体内抗肿瘤实验表明，金-牛血清白蛋白-DOX-FA纳米复合材料对过表达FR的肿瘤具有选择性抗肿瘤活性，对正常组织和器官没有不良影响。总之，金-牛血清白蛋白-DOX-FA纳米复合材料表现出选择性靶向活性、X射线衰减活性和pH敏感的药物释放活性。因此，它可以增强CT成像并提高过表达FR的胃癌的靶向治疗效果。我们的研究结果表明，金-牛血清白蛋白-DOX-FA纳米复合材料是一种新型的药物递送载体，是癌症诊疗应用中有前景的候选物。
