Co-Delivery of NIR-II Semiconducting Polymer and pH-Sensitive Doxorubicin-Conjugated Prodrug for Photothermal/Chemotherapy

Abstract

Semiconducting polymer (SP) is a promising photothermal agent in antitumor application, but co-delivery of NIR-II SPs with chemotherapeutic drug remains a challenge. Here, SPs was firstly improved via backbone and alky side chain engineering, and afterward SPs and pH-sensitive prodrug copolymer PEG-PAsp(BzA- co -DIP- co -DOX) assembled into a nanoparticle PADD@SPs for photoacoustic (PA)-imaging guided combination of photothermal therapy and chemotherapy. SPs-encapsulated nanoparticles PADD@SPs exhibited a high photothermal conversion efficiency of ~48% at a relatively low power level of NIR irradiation (0.3 W/cm 2 for 5 min). DOX was rapidly released from nanoparticles in response to acidic environment within lysosome. PA and fluorescence imaging confirmed that photothermal therapy effectively drove DOX penetration inside tumor tissue, killing tumor cells survived from hyperthermia. The synergistic effect of SPs-based photothermal therapy and DOX-induced chemotherapy was verified in vivo. Overall, co-delivery of the SP and DOX using pH-sensitive nanoparticles represents a feasible strategy for photothermal therapy with potentially synergistic drug effects.

Keywords: NIR II photothermal therapy; Semiconducting polymer; co-delivery; pHsensitive drug release; Doxorubicin; Combined therapy