An ultrasmall PVP-Fe-Cu-Ni-S nano-agent for synergistic cancer therapy through triggering ferroptosis and autophagy

Photothermal therapy (PTT) is an emerging field where photothermal agents could convert visible or near-infrared (NIR) radiation into heat to kill tumor cells. However, the low photothermal conversion efficiency of photothermal agents and their limited antitumor activities hinder the development of these agents into monotherapies for cancer. Herein, we have fabricated an ultrasmall polyvinylpyrrolidone (PVP)-Fe-Cu-Ni-S (PVP-NP) nano-agent via a simple hot injection method with excellent photothermal conversion efficiency (& SIM;96%). Photothermal therapy with this nano-agent effectively inhibits tumor growth without apparent toxic side-effects. Mechanistically, our results demonstrated that, after NIR irradiation, PVP-NPs can induce ROS/singlet oxygen generation, decrease the mitochondrial membrane potential, release extracellular Fe2+, and consume glutathione, triggering autophagy and ferroptosis of cancer cells. Moreover, PVP-NPs exhibit excellent contrast enhancement according to magnetic resonance imaging (MRI) analysis. In summary, PVP-NPs have a high photothermal conversion efficiency and can be applied for MRI-guided synergistic photothermal/photodynamic/chemodynamic cancer therapy, resolving the bottleneck of existing phototherapeutic agents.

Automated summary

Photothermal therapy (PTT) is a promising approach for killing tumor cells by converting radiation into heat. However, the low efficiency and limited antitumor activities of photothermal agents restrict their development as monotherapies for cancer. In this study, an ultrasmall PVP-Fe-Cu-Ni-S nano-agent with excellent photothermal conversion efficiency was successfully fabricated. Photothermal therapy using this nano-agent effectively inhibited tumor growth without toxic side-effects. Mechanistically, the nano-agent induced ROS generation, triggered autophagy and ferroptosis of cancer cells, and showed excellent contrast enhancement in MRI analysis. Overall, PVP-NPs have great potential for synergistic photothermal/photodynamic/chemodynamic cancer therapy and can overcome the limitations of existing phototherapeutic agents.