Multifunctional Near Infrared Polymer Dots for Enhanced Synergistic Photodynamic/Photothermal Effect In Vitro

Synergistic photodynamic/photothermal therapy (PDT/PTT) can be used to target cancer cells by locally generating singlet oxygen species or increasing temperature under laser irradiation. This approach offers higher tumor ablation efficiency, lower therapeutic dose requirements, and reduced side effects compared to single treatment approaches. However, the therapeutic efficiency of PDT/PTT is still limited by the low oxygen levels within the solid tumors caused by abnormal vasculature and altered cancer cell metabolism. To address these challenges, we developed multifunctional nanoparticles with high catalytic activity for converting tumor hydrogen peroxide (H2O2) into oxygen (O2). Using poly(styrene-co-maleic anhydride) (PSMA) as a cross-linker, we generated compact, highly fluorescent Pdots, used poly[2,6-(4,4-bis(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) as a near-infrared photosensitizer for both photodynamic and photothermal applications, and incorporated manganese (Mn) ions to catalyze the H2O2-to-O2 conversion. These Mn-doped Pdots significantly enhance O2 production, achieving an enhanced 1O2 quantum yield from 0.46 to 0.64 with the addition of H2O2, achieving the goal of improving PDT efficiency. With this rational design, we produced Pdots with enhanced H2O2-to-1O2 converting ability for potential use in PDT. For photothermal applications, our Pdots generate a photothermal conversion efficiency of 53%. In vitro studies using human MCF7 adenocarcinoma cells confirmed the biocompatibility of these Pdots in the absence of laser exposure with a pronounced cell killing effect under laser irradiation for synergistic PDT/PTT. These results highlight the promise of Pdots in overcoming oxygen limitations, balancing the performance of PDT/PTT, and enhancing the therapeutic efficacy of PDT/PTT in cancer cells in vitro.