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.