Department of General Surgery, Zhujiang Hospital, Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Department of Cardiology, Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Translational Medicine Research Center, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
J Nanobiotechnology. 2024 May 29;22(1):297. doi: 10.1186/s12951-024-02566-6.
Chemotherapy, as a conventional strategy for tumor therapy, often leads to unsatisfied therapeutic effect due to the multi-drug resistance and the serious side effects. Herein, we genetically engineered a thermal-responsive murine Ferritin (mHFn) to specifically deliver mitoxantrone (MTO, a chemotherapeutic and photothermal agent) to tumor tissue for the chemotherapy and photothermal combined therapy of colorectal cancer, thanks to the high affinity of mHFn to transferrin receptor that highly expressed on tumor cells. The thermal-sensitive channels on mHFn allowed the effective encapsulation of MTO in vitro and the laser-controlled release of MTO in vivo. Upon irradiation with a 660 nm laser, the raised temperature triggered the opening of the thermal-sensitive channel in mHFn nanocage, resulting in the controlled and rapid release of MTO. Consequently, a significant amount of reactive oxygen species was generated, causing mitochondrial collapse and tumor cell death. The photothermal-sensitive controlled release, low systemic cytotoxicity, and excellent synergistic tumor eradication ability in vivo made mHFn@MTO a promising candidate for chemo-photothermal combination therapy against colorectal cancer.
化疗作为肿瘤治疗的常规策略，由于多药耐药性和严重的副作用，往往导致治疗效果不理想。在此，我们通过基因工程技术构建了一种热响应型鼠铁蛋白（mHFn），该蛋白能够特异性地将米托蒽醌（MTO，一种化疗药物和光热试剂）递送至肿瘤组织，用于结直肠癌的化疗和光热联合治疗，这要归功于 mHFn 与转铁蛋白受体的高亲和力，转铁蛋白受体在肿瘤细胞中高度表达。mHFn 上的热敏感通道允许 MTO 的有效包封在体外和激光控制的释放 MTO 在体内。当用 660nm 激光照射时，升高的温度触发 mHFn 纳米笼中热敏感通道的打开，导致 MTO 的受控和快速释放。结果，产生了大量的活性氧，导致线粒体崩溃和肿瘤细胞死亡。光热敏感的控制释放、低全身细胞毒性以及体内优异的协同肿瘤消除能力使 mHFn@MTO 成为用于结直肠癌化疗-光热联合治疗的有前途的候选药物。
