Nanodrug Hijacking Blood Transferrin for Ferroptosis-Mediated Cancer Treatment

Ferroptosis as a promising method of cancer treatment heavily relies on the intracellular iron ion level. Herein, a new iron-supplement nanodrug was developed by conjugating transferrin-homing peptide T₁₀ on the surface of cross-linked lipoic acid vesicles (T₁₀@cLAV), which could hijack blood transferrin (Tf) and specifically deliver it to tumor cells to elevate the Fe²⁺ level. Meanwhile, the intracellular degradation product of cLAV, dihydrolipoic acid, could regenerate Fe²⁺ to further boost the ferroptosis. The results disclosed that T₁₀@cLAV achieved tumor inhibition comparable to that of cisplatin at a dose as low as 5 mg/kg in the HeLa tumor-bearing nude mice model and caused no toxicity at the dose up to 300 mg/kg. This tactful iron-supplement strategy of hijacking blood Tf is superior to the current strategies: one is the induction of intracellular ferritin degradation, which is limited by the low content of ferritin, and the other is the delivery of iron-based materials, which easily causes adverse effects.