化疗作为肿瘤治疗的常规策略，由于其多重耐药性和严重的副作用，往往导致治疗效果不理想。在此，我们通过基因工程改造了热响应性鼠铁蛋白（mHFn），利用mHFn与转铁蛋白的高亲和力，将米托蒽醌（MTO，一种化疗和光热剂）特异性递送至肿瘤组织，用于结直肠癌的化疗和光热联合治疗肿瘤细胞上高表达的受体。 mHFn 上的热敏通道可以在体外有效封装 MTO，并在体内激光控制释放 MTO。在 660 nm 激光照射下，升高的温度触发 mHFn 纳米笼中热敏通道的打开，从而导致 MTO 的受控和快速释放。因此，产生了大量的活性氧，导致线粒体崩溃和肿瘤细胞死亡。光热敏感的控释、低全身细胞毒性和出色的体内协同肿瘤根除能力使 mHFn@MTO 成为结直肠癌化疗光热联合疗法的有前途的候选者。© 2024。作者。

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.© 2024. The Author(s).