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 (HO) into oxygen (O). Using poly(styrene--maleic anhydride) (PSMA) as a cross-linker, we generated compact, highly fluorescent Pdots, used poly[2,6-(4,4-bis(2-ethylhexyl)-4-cyclopenta[2,1-;3,4-']dithiophene)--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 HO-to-O conversion. These Mn-doped Pdots significantly enhance O production, achieving an enhanced O quantum yield from 0.46 to 0.64 with the addition of HO, achieving the goal of improving PDT efficiency. With this rational design, we produced Pdots with enhanced HO-to-O converting ability for potential use in PDT. For photothermal applications, our Pdots generate a photothermal conversion efficiency of 53%. 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 .