NIR‐II Light Accelerated Prodrug Reduction of Pt(IV)‐Incorporating Pseudo Semiconducting Polymers for Robust Degradation and Maximized Photothermal/Chemo‐Immunotherapy

Abstract Selective activation of Pt(IV) prodrugs within tumors is particularly attractive because of their low damage to normal tissues. However, current common activation via chemical/photoreduction of Pt(IV) prodrugs into Pt(II) counterparts is limited by undesirable spatial–temporal control over this reduction process and the ineffective tissue penetration depth of undesirable light. Here, a pseudo‐conjugated‐polymer is designed via Stille polymerization, resulting in PSP‐Pt with a Pt(IV) prodrug of oxaliplatin (Oxa(IV)) in the polymer main chain that can be activated by NIR‐II light. PSP‐Pt can co‐assemble with a commercially available lipid polymer, namely mPEG_2k‐DSPE, into NP^PSP‐Pt. Under 1064 nm light irradiation, NP^PSP‐Pt can be photoactivated to accelerate the Pt(IV) reduction to release oxaliplatin, thereby killing the cancer cells by photothermal effect and chemo‐immunotherapy inside a mouse model with CT26 colon cancer. This work reports the application of NIR‐II light for accelerating Pt(IV) reduction for cancer tumor therapy.