Tong Chunyi, Zhang Xizhi, Fan Jialong, Li Bin, Liu Bin, Daniyal Muhammad, Wang Wei
College of Biology, Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, Hunan University, Changsha 410082, China.
TCM and Ethnomedicine Innovation & Development Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.
Sci Bull (Beijing). 2018 Jul 30;63(14):935-946. doi: 10.1016/j.scib.2018.06.003. Epub 2018 Jun 7.
Despite chemotherapy has been widely used for tumor therapy, the serious side effect is still a major challenge. Recently, two dimensional nanomaterial-based drug delivery systems have attracted wide concern due to their high drug loading and low side effect. In addition, some kinds of nanomaterials can directly act as a photosensitizer to induce cancer destruction. In this study, we developed a drug delivery system of mixture of high/low molecular weight branched polyethylenimine-polyethylene glycol-reduced graphene oxide (mBPEI-PEG-rGO) using reduced graphene oxide as matrix. A model drug of doxorubicin (DOX) was loaded on the nanocomposites with the efficiency of 81% and the release rate of more than 50% at acidic environment. In vitro experiments indicated that mBPEI-PEG-rGO-DOX with enhanced stability and biocompatibility efficiently delivered and released DOX into cells mainly through micropinocytosis and killed SMMC-7721 cells by inducing reactive oxygen species (ROS) and cell apoptosis. Furthermore, in vivo experiments indicated that the combination of intratumoral injection of mBPEI-PEG-rGO-DOX and local laser irradiation nearly ablated hepatocarcinoma. In conclusion, this new drug delivery system provided an alternative for combinational photothermal and chemotherapy against hepatocarcinoma.
尽管化疗已广泛用于肿瘤治疗，但严重的副作用仍是一个重大挑战。近年来，基于二维纳米材料的药物递送系统因其高载药量和低副作用而备受关注。此外，某些纳米材料可直接作为光敏剂诱导癌症破坏。在本研究中，我们以还原氧化石墨烯为基质，开发了一种由高/低分子量支化聚乙烯亚胺-聚乙二醇-还原氧化石墨烯（mBPEI-PEG-rGO）组成的药物递送系统。将阿霉素（DOX）作为模型药物负载到纳米复合材料上，负载效率为81%，在酸性环境下释放率超过50%。体外实验表明，具有增强稳定性和生物相容性的mBPEI-PEG-rGO-DOX主要通过微胞饮作用有效地将DOX递送至细胞并释放到细胞中，并通过诱导活性氧（ROS）和细胞凋亡杀死SMMC-7721细胞。此外，体内实验表明，瘤内注射mBPEI-PEG-rGO-DOX与局部激光照射相结合几乎可消除肝癌。总之，这种新型药物递送系统为肝癌的光热联合化疗提供了一种替代方案。
