Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China.
Biomater Sci. 2019 Jun 25;7(7):2951-2960. doi: 10.1039/c9bm00342h.
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.
最近，由于具有可控的生物降解性和优异的载药能力，嵌段共聚物胶束受到了广泛关注。不幸的是，载药胶束的体内稳定性差和递送效率低极大地阻碍了其在生物医学中的应用。在此，我们开发了一种新型的可生物降解的载磁铁/阿霉素（Fe3O4/DOX）的聚乙二醇化有机硅纳米胶束（命名为 FDPOMs），其具有高循环稳定性和智能 GSH 触发的生物降解性，可用于磁共振成像（MRI）和肿瘤化疗的磁性靶向。FDPOMs 通过可生物降解的聚己内酯嵌段聚（谷氨酸）（PCL-b-PGA）、化疗药物阿霉素（DOX）和 Fe3O4 纳米粒子在油/水体系中的自组装，随后用 3-巯丙基三甲氧基硅烷（MPTMS）分子进行有机硅交联和表面聚乙二醇化制备而成。所得的 FDPOMs 在生物介质中表现出优异的分散性和稳定性，具有显著的 T2 加权磁共振成像能力、独特的 GSH 响应释放行为以及对肿瘤细胞的选择性毒性。体内实验表明，FDPOMs 不仅具有改善的磁共振肿瘤成像能力，而且由于在外磁场下具有强大的磁性靶向能力，还表现出了高的抗肿瘤疗效。因此，FDPOMs 是用于磁性靶向 MRI 和成像引导肿瘤化疗的有前途的候选物。
