Cationic Polymer-Photothermal Agent Conjugates with Enhanced Light Absorption and Tumor Accumulation for Efficient Phototherapy of Osteosarcoma.

Abstract

The development of nanoanticancer agents has garnered significant interest, particularly for their application in the second near-infrared (NIR-II) phototherapy. Despite the promise that nanoparticles hold for tumor phototherapy, their limited light absorption efficiency and tumor accumulation ability substantially constrain their effectiveness in practical applications. This necessitates not only a profound comprehension of nanoparticle properties but also an intricate understanding of their targeting/delivery mechanisms. In this study, we showcase the impressive outcomes achieved by combining small molecular photothermal agents (PTAs) with cationic polymer (<b>PWS5@NPs</b>). By harnessing the exceptional NIR-II photothermal properties of aza-boron-dipyrromethene (aza-BODIPY) derivatives and the protonation/deprotonation characteristics of <i>N</i>,<i>N</i>-dimethyl acrylamide (<b>PA1</b>), we have successfully engineered multifunctional nanoparticles that facilitate efficient in situ enrichment of osteosarcoma via active endocytosis. Furthermore, molecular self-assembly reduces the size of the nanoparticles and diminishes the interactions between aza-BODIPY molecules within the polymer matrix, markedly improving the light absorption efficiency of the nanoparticles. This cationic polymer-photothermal agent conjugate design not only amplifies the fluorescence brightness of the nanoparticles but also enhances the photothermal therapy (PTT) efficacy against in situ osteosarcoma.