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已发表论文
具有屏蔽和刺激响应释放特性的锰生物矿化铁蛋白纳米平台用于增强铁死亡和多模态卵巢癌治疗
Authors Chen D, Zheng X, Gao Q, Chen B , Sun Y
Received 20 June 2025
Accepted for publication 12 January 2026
Published 21 January 2026 Volume 2026:21 548411
DOI https://doi.org/10.2147/IJN.S548411
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr RDK Misra
Dezhao Chen,1– 3,* Xiaohan Zheng,2,3,* Qiao Gao,3,4,* Bing Chen,3,5 Yang Sun1,3
1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Obstetrics & Gynecology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Obstetrics & Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian Province, People’s Republic of China; 5School of Medical Imaging, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yang Sun, Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China, Email sunyang@fjmu.edu.cn Bing Chen, Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China, Email BingChen_001@126.com; BingChen_001@fjmu.edu.cn
Purpose: Natural ferritin Fn) is a cage-like protein with a central cavity, making it a promising vehicle for drug delivery. However, its non-specific accumulation in iron-metabolizing organs impairs targeting precision and therapeutic efficacy. To overcome this challenge, we aimed to develop a novel biomimetic nanoplatform based on manganese-mineralized ferritin loaded with dihydroartemisinin (DHA@MFn) for precise ovarian cancer treatment, enabling controlled drug release and amplified therapeutic effects within the tumor microenvironment.
Methods: We constructed a manganese-mineralized ferritin nanocage encapsulating DHA, resulting in DHA@MFn with favorable physicochemical properties, including a particle size of 12.2 nm and a zeta potential of − 13.54 mV. The stability, stimuli-responsiveness, and in vitro release behavior of DHA@MFn were evaluated under weakly acidic conditions. We assessed its ability to catalyze Fenton-like reactions releasing Mn2+, induce ferroptosis via lipid peroxidation and GSH depletion, and enable controlled drug release. In vivo biodistribution, tumor accumulation, and therapeutic efficacy were investigated using SKOV3 tumor-bearing mice, alone and in combination with irradiation.
Results: DHA@MFn remained stable and demonstrated excellent responsiveness to the tumor microenvironment, releasing Mn2+ ions that catalyzed Fenton-like reactions for hydroxyl radical production. The nanoplatform facilitated targeted tumor accumulation and retention, significantly reducing off-target organ distribution, particularly in the liver. The release of DHA induced ferroptosis through lipid peroxidation and GSH depletion, enhancing oxidative stress. Combined with irradiation, DHA@MFn achieved superior tumor ablation through synergistic ferroptosis, photothermal effects, and minimal systemic toxicity compared to free DHA, MFn alone, or their combinations with irradiation.
Conclusion: This multifunctional biomimetic nanoplatform presents a promising strategy for precise, multimodal ovarian cancer therapy. By integrating controlled drug delivery, catalytic Fenton-like reactions, and synergistic radiotherapy, DHA@MFn demonstrates significant potential for clinical translation in targeted cancer treatment.
Keywords: ferritin, biomineralization, ferroptosis, synergistic therapy, ovarian cancer
1Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China; 2Department of Obstetrics & Gynecology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, People’s Republic of China; 3Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China; 4Department of Obstetrics & Gynecology, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian Province, People’s Republic of China; 5School of Medical Imaging, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yang Sun, Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian Province, People’s Republic of China, Email sunyang@fjmu.edu.cn Bing Chen, Key Laboratory of Nanomedical Technology (Education Department of Fujian Province), Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China, Email BingChen_001@126.com; BingChen_001@fjmu.edu.cn
Purpose: Natural ferritin Fn) is a cage-like protein with a central cavity, making it a promising vehicle for drug delivery. However, its non-specific accumulation in iron-metabolizing organs impairs targeting precision and therapeutic efficacy. To overcome this challenge, we aimed to develop a novel biomimetic nanoplatform based on manganese-mineralized ferritin loaded with dihydroartemisinin (DHA@MFn) for precise ovarian cancer treatment, enabling controlled drug release and amplified therapeutic effects within the tumor microenvironment.
Methods: We constructed a manganese-mineralized ferritin nanocage encapsulating DHA, resulting in DHA@MFn with favorable physicochemical properties, including a particle size of 12.2 nm and a zeta potential of − 13.54 mV. The stability, stimuli-responsiveness, and in vitro release behavior of DHA@MFn were evaluated under weakly acidic conditions. We assessed its ability to catalyze Fenton-like reactions releasing Mn2+, induce ferroptosis via lipid peroxidation and GSH depletion, and enable controlled drug release. In vivo biodistribution, tumor accumulation, and therapeutic efficacy were investigated using SKOV3 tumor-bearing mice, alone and in combination with irradiation.
Results: DHA@MFn remained stable and demonstrated excellent responsiveness to the tumor microenvironment, releasing Mn2+ ions that catalyzed Fenton-like reactions for hydroxyl radical production. The nanoplatform facilitated targeted tumor accumulation and retention, significantly reducing off-target organ distribution, particularly in the liver. The release of DHA induced ferroptosis through lipid peroxidation and GSH depletion, enhancing oxidative stress. Combined with irradiation, DHA@MFn achieved superior tumor ablation through synergistic ferroptosis, photothermal effects, and minimal systemic toxicity compared to free DHA, MFn alone, or their combinations with irradiation.
Conclusion: This multifunctional biomimetic nanoplatform presents a promising strategy for precise, multimodal ovarian cancer therapy. By integrating controlled drug delivery, catalytic Fenton-like reactions, and synergistic radiotherapy, DHA@MFn demonstrates significant potential for clinical translation in targeted cancer treatment.
Keywords: ferritin, biomineralization, ferroptosis, synergistic therapy, ovarian cancer