Manganese Biomineralized Ferritin Nanoplatforms with Shielding and Stimuli-Responsive Release for Potentiated Ferroptosis and Multimodal Ovarian Cancer Therapy.

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 Mn Results: DHA@MFn remained stable and demonstrated excellent responsiveness to the tumor microenvironment, releasing Mn 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.