Biomimic FeS2 nanodrug with hypothermal photothermal effect by clinical approved NIR-Ⅱ light for augmented chemodynamic therapy

Hypothermal photothermal therapy (HPTT) employs hyperthermia (<45 °C) to destroy tumor cells with negligible side effects to the surrounding normal tissues. Despite extensive studies, the clinical translation of HPTT is severely hindered, owing to the discounted therapeutic effect and maximum permissible power of near-infrared (NIR) laser by food and drug administration (FDA). Herein, we report a rational design of red blood cell membranes (RBCs) coated FeS 2 (FeS 2 @RBCs) with strong absorption at NIR-Ⅱ window for effective HPTT augmented chemodynamic therapy (CDT). FeS 2 @RBCs exhibits prolonged blood circulation and negligible immune response, leading to improved tumor accumulation for enhanced HPTT. Furthermore, the CDT effect of FeS 2 @RBCs is significantly augmented by the temperature elevation in the tumor region, which leads to the synergetic HPTT and CDT. Lipidomics analysis reveals that the damage of tumor cells by CDT is via the lipid peroxidation. In addition, FeS 2 @RBCs exhibits self-enhanced magnetic resonance imaging after reacting with H 2 O 2 in tumor region for imaging-guided laser irradiation. Thus, FeS 2 @RBCs achieves remarkable inhibition of subcutaneous 4T1 breast tumor growth without obvious side effects by a 1064 nm laser irradiation of 1.0 W/cm 2 (FDA approved power density). Overall, this work provides a HPTT augmented CDT strategy for effective cancer therapy with a clinical approved laser power, which may pave the way for the clinical application of HPTT augmented CDT in the future.