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

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/photo-reduction 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 was 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 photo-activated 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 the first time for accelerating Pt(IV) reduction for cancer tumor therapy. This article is protected by copyright. All rights reserved.