Laser-activable murine ferritin nanocage for chemo-photothermal therapy of colorectal cancer

• Published in: Journal of nanobiotechnology Vol. 22; no. 1; pp. 297 - 15
• Main Authors: Cheng, Jinmei, Li, Jiaxin, Yu, Qilin, Li, Peishan, Huang, Junyi, Li, Jinhui, Guan, Leyang, Xu, Zhiyong, Xiao, Jisheng, Duan, Xiaopin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.05.2024; BioMed Central; BMC
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cancer; Care and treatment; Cell death; Cell Line, Tumor; Chemo-photothermal therapy; Chemotherapy; Chemotherapy, Combination; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - therapy; Dosage and administration; Drug delivery systems; Drug resistance; Drugs; Female; Ferritin; Ferritins - chemistry; Ferritins - metabolism; Genetic engineering; Genetically modified organisms; Health aspects; Humans; Lasers; Methods; Mice; Mice, Inbred BALB C; Mice, Nude; Mitoxantrone; Mitoxantrone - chemistry; Mitoxantrone - pharmacology; Mitoxantrone - therapeutic use; Mitoxantrone hydrochloride; Murine ferritin nanocage; Nanomedicine; Phototherapy; Photothermal Therapy - methods; Product information; Reactive Oxygen Species - metabolism; Therapeutics, Experimental; Thermal-responsive; Tumors; Vehicles; China; Murine ferritin nanocage; Thermal-responsive; Mitoxantrone; Chemo-photothermal therapy; Colorectal cancer
• ISSN: 1477-3155; 1477-3155
• 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.