Cheng Mo, Yu Yan, Huang Wending, Fang Meng, Chen Yong, Wang Chunmeng, Cai Weiluo, Zhang Shuyu, Wang Wenxing, Yan Wangjun
Department of Musculoskeletal Surgery of Shanghai Cancer Center, Fudan University, Dong'an Road, Shanghai 200032, China PR.
Engineering Research Center of Advanced Lighting Technology, Ministry of Education, Institute for Electric Light Sources, and Academy for Engineering and Technology, Fudan University, Shanghai 200433, China PR.
ACS Biomater Sci Eng. 2020 Sep 14;6(9):4985-4992. doi: 10.1021/acsbiomaterials.0c00507. Epub 2020 Aug 3.
The development of new nanocarriers with desired degradability and targeted ability is of great significance for efficient drug delivery. In this work, a monodisperse hollow structured MnO (H-MnO) with a mesoporous shell is prepared and functionalized for efficient targeted drug delivery. The highly monodisperse H-MnO with a uniform morphology was obtained by growing MnO on solid silica nanoparticles and subsequently removing the silica core. Then, the H-MnO is successively modified with polyethylene glycol and targeted molecule folate (FA). The resultant H-MnO-FA shows excellent colloidal stability and high drug-loading content (∼58.2%) of the antitumor drug doxorubicin hydrochloride (DOX). The H-MnO-FA possesses acid-responsive T-weighted magnetic resonance imaging ability. The pH-dependent biodegradation behavior of H-MnO-FA is directly observed in vitro and confirmed by imaging, which is expected to favor the potential clearance of this hollow structured nanocarrier and eliminate its long-term toxicity. In addition, the DOX-loaded H-MnO-FA also demonstrates excellent cancer cell-killing effect and tumor inhibition efficacy.
开发具有所需可降解性和靶向能力的新型纳米载体对于高效药物递送具有重要意义。在这项工作中,制备了一种具有介孔壳的单分散中空结构MnO(H-MnO)并对其进行功能化以实现高效靶向药物递送。通过在固体二氧化硅纳米颗粒上生长MnO并随后去除二氧化硅核心,获得了具有均匀形态的高度单分散H-MnO。然后,H-MnO依次用聚乙二醇和靶向分子叶酸(FA)进行修饰。所得的H-MnO-FA表现出优异的胶体稳定性和抗肿瘤药物盐酸阿霉素(DOX)的高载药量(约58.2%)。H-MnO-FA具有酸响应性T加权磁共振成像能力。通过成像在体外直接观察到H-MnO-FA的pH依赖性生物降解行为,并得到证实,这有望有利于这种中空结构纳米载体的潜在清除并消除其长期毒性。此外,负载DOX的H-MnO-FA还表现出优异的癌细胞杀伤效果和肿瘤抑制功效。