• Isorhamnetin preconditioning enhances the therapeutic efficacy of MSC-derived exosomes against chemotherapy-induced premature ovarian failure.
• ISO-MSC-Exos suppress ferroptosis by downregulating Alox15 and Tf, reducing lipid peroxidation and iron uptake.
• ISO-MSC-Exos restore ovarian function, hormone levels, and fertility more effectively than unmodified MSC-Exos.
• Targeting ferroptosis via engineered exosomes represents a promising strategy for treating POF.