Sha Zhou, Yang Shuguang, Fu Liwen, Geng Mengru, Gu Jiani, Liu Xuying, Li Shikai, Zhou Xiaojun, He Chuanglong
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.
Nanoscale. 2021 Mar 12;13(9):5077-5093. doi: 10.1039/d0nr09220g.
In this study, an effective and facile strategy is reported to construct a multifunctional nanoplatform by in situ doping metal manganese on gold core mesoporous silica nanoparticles (Au@MMSN). After further modification of alendronate (Ald) on Au@MMSN, the obtained Au@MMSN-Ald efficiently integrates bone targeted chemo-chemodynamic combination therapy and dual-modality computed tomography/magnetic resonance (CT/MR) imaging into a single platform. In particular, Au@MMSN-Ald exhibits excellent tumor microenvironment responsive drug release efficiency. The doxorubicin hydrochloride (DOX) loaded Au@MMSN-Ald (DOX@Au@MMSN-Ald) is demonstrated with excellent targeted ability toward osteosarcoma. Accordingly, in a specific tumor microenvironment, DOX@Au@MMSN-Ald also displays outstanding combined efficiency for killing cancer cells in vitro and suppressing the osteosarcoma growth in vivo. Benefiting from the Au nanoparticles confined in the core and manganese ions released from the shell, CT and MR dual-modality imaging were performed to verify the effective accumulation of Au@MMSN-Ald at the tumor site. Overall, the constructed DOX@Au@MMSN-Ald nanoparticles integrated imaging guide, responsive drug release and combination therapy, which may provide some insight for further biomedical applications in efficient osteosarcoma therapy.
在本研究中,报道了一种有效且简便的策略,即通过在金核介孔二氧化硅纳米颗粒(Au@MMSN)上原位掺杂金属锰来构建多功能纳米平台。在Au@MMSN上进一步修饰阿仑膦酸盐(Ald)后,所得的Au@MMSN-Ald将骨靶向化学-化学动力学联合疗法和双模态计算机断层扫描/磁共振(CT/MR)成像有效地整合到单个平台中。特别地,Au@MMSN-Ald表现出优异的肿瘤微环境响应性药物释放效率。负载盐酸阿霉素(DOX)的Au@MMSN-Ald(DOX@Au@MMSN-Ald)对骨肉瘤具有优异的靶向能力。因此,在特定的肿瘤微环境中,DOX@Au@MMSN-Ald在体外杀死癌细胞和体内抑制骨肉瘤生长方面也表现出出色的联合效率。受益于限制在核心中的金纳米颗粒和从壳层释放的锰离子,进行了CT和MR双模态成像以验证Au@MMSN-Ald在肿瘤部位的有效积累。总体而言,构建的DOX@Au@MMSN-Ald纳米颗粒整合了成像引导、响应性药物释放和联合疗法,这可能为骨肉瘤高效治疗的进一步生物医学应用提供一些见解。