Biodegradable organosilica magnetic micelles for magnetically targeted MRI and GSH-triggered tumor chemotherapy
Biodegradable organosilica magnetic micelles for magnetically targeted MRI and GSH-triggered tumor chemotherapy
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用于磁靶向 MRI 和 GSH 触发肿瘤化疗的可生物降解有机硅磁性胶束
DOI：
10.1039/c9bm00342h
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发表时间：
2019
影响因子：
6.6
通讯作者：
Li Yongsheng
中科院分区：
文献类型：
--
作者：
Yang Tiangang;Niu Dechao;Chen Jianzhuang;He Jianping;Yang Shaobo;Jia Xiaobo;Hao Jina;Zhao Wenru;Li Yongsheng
近年来，嵌段共聚物胶束由于其可控的生物降解性和优异的负载能力而受到广泛关注。然而，载药胶束在体内的稳定性差、释药效率低，极大地限制了其在生物医学领域的应用。在此，我们开发了一种新的可生物降解的磁铁矿/阿霉素（Fe 3 O 4/DOX）共负载PEG化有机硅胶束（指定为FDPOM），具有高循环稳定性和智能GSH触发的生物降解性，用于磁靶向磁共振成像（MRI）和肿瘤化疗。通过生物可降解的聚己内酯-嵌段-聚谷氨酸（PCL-b-PGA）、化疗药物DOX和Fe 3 O 4纳米粒子在油/水体系中自组装，随后与3-巯基丙基三甲氧基硅烷（MPTMS）分子交联并表面聚乙二醇化制备FDPOM。所得FDPOM在生物介质中表现出优异的分散性和稳定性，显著的T2加权MR成像能力，独特的GSH响应性释放行为和对肿瘤细胞的选择性毒性。体内实验表明，FDPOM不仅具有改善的MR肿瘤成像能力，而且由于在外磁场下的强磁靶向能力而表现出高的抗肿瘤功效。因此，FDPOM是磁靶向MR成像和成像引导的肿瘤化疗的有希望的候选者。
Recently, block copolymer micelles have attracted widespread attention due to their controlled biodegradability and excellent loading capability. Unfortunately, the poor in vivo stability and low delivery efficiency of drug-loaded micelles greatly hampered their biomedical applications. Herein, we develop a new kind of biodegradable magnetite/doxorubicin (Fe3O4/DOX) co-loaded PEGylated organosilica micelles (designated as FDPOMs) with both high circulating stability and smart GSH-triggered biodegradability for magnetically targeted magnetic resonance imaging (MRI) and tumor chemotherapy. The FDPOMs are prepared by the self-assembly of biodegradable polycaprolactone-block-poly(glutamic acid) (PCL-b-PGA), a chemotherapeutic DOX drug and Fe3O4 nanoparticles in an oil/water system, subsequent organosilica cross-linking with 3-mercaptopropyltrimethoxysilane (MPTMS) molecules and surface PEGylation. The resultant FDPOMs exhibit excellent dispersity and stability in biological media, remarkable T2-weighted MR imaging capability, unique GSH-responsive release behavior and selective toxicity to tumor cells. The in vivo experiments show that the FDPOMs not only have improved MR tumor imaging capability, but also exhibit high anti-tumor efficacy due to the strong magnetic targeting ability under an external magnetic field. Consequently, the FDPOMs are promising candidates for magnetically targeted MR imaging and imaging-guided tumor chemotherapy.