Xiao Hui-Fang, Yu Hui, Wang De-Qiang, Liu Xin-Zheng, Sun Wan-Ru, Li You-Jie, Sun Guang-Bin, Liang Yan, Sun Hong-Fang, Wang Ping-Yu, Xie Shu-Yang, Wang Ran-Ran
Institute of Rehabilitation Medicine, School of Rehabilitation Medicine, Binzhou Medical University, Yantai, 264003, PR China.
Binzhou Medical University Hospital, Binzhou, 256603, PR China.
J Biomed Nanotechnol. 2022 Feb 1;18(2):352-368. doi: 10.1166/jbn.2022.3254.
The construction of high-efficiency tumor theranostic platform will be of great interest in the treatment of cancer patients; however, significant challenges are associated with developing such a platform. In this study, we developed high-efficiency nanotheranostic agent based on ferroferric oxide, manganese dioxide, hyaluronic acid and doxorubicin (FMDH-D NPs) for dual targeting and imaging guided synergetic photothermal-enhanced chemodynamic/chemotherapy for cancer, which improved the specific uptake of drugs at tumor site by the dual action of CD44 ligand hyaluronic acid and magnetic nanoparticles guided by magnetic force. Under the acidic microenvironment of cancer cells, FMDH-D could be decomposed into Mn and Fe to generate •OH radicals by triggering a Fenton-like reaction and responsively releasing doxorubicin to kill cancer cells. Meanwhile, alleviating tumor hypoxia improved the efficacy of chemotherapy in tumors. The photothermal properties of FMDH generated high temperatures, which further accelerated the generation of reactive oxygen species, and enhanced effects of chemodynamic therapy. Furthermore, FMDH-D NPs proved to be excellent T/T₂-weighted magnetic resonance imaging contrast agents for monitoring the tumor location. These results confirmed the considerable potential of FMDH-D NPs in a highly efficient synergistic therapy platform for cancer treatment.
构建高效的肿瘤诊疗平台在癌症患者治疗中具有重大意义;然而,开发这样一个平台存在重大挑战。在本研究中,我们基于四氧化三铁、二氧化锰、透明质酸和阿霉素开发了高效纳米诊疗剂(FMDH-D NPs),用于癌症的双靶向和成像引导协同光热增强化学动力学/化疗,通过CD44配体透明质酸和磁力引导的磁性纳米颗粒的双重作用提高了肿瘤部位药物的特异性摄取。在癌细胞的酸性微环境下,FMDH-D可分解为锰和铁,通过引发类芬顿反应产生活性氧自由基,并响应性释放阿霉素以杀死癌细胞。同时,缓解肿瘤缺氧提高了肿瘤化疗的疗效。FMDH的光热特性产生高温,进一步加速了活性氧的产生,增强了化学动力学治疗效果。此外,FMDH-D NPs被证明是用于监测肿瘤位置的优异T/T₂加权磁共振成像造影剂。这些结果证实了FMDH-D NPs在高效协同治疗癌症的平台中具有巨大潜力。