Wu Yingfen, Darland Diane C, Combs Colin K, Zhao Julia Xiaojun
Department of Chemistry, University of North Dakota, Grand Forks, North Dakota 58202, United States.
Department of Biology, University of North Dakota, Grand Forks, North Dakota 58202, United States.
ACS Appl Bio Mater. 2025 Feb 17;8(2):1278-1291. doi: 10.1021/acsabm.4c01593. Epub 2025 Jan 22.
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 .
协同光动力/光热疗法（PDT/PTT）可通过在激光照射下局部产生活性单线态氧或升高温度来靶向癌细胞。与单一治疗方法相比，这种方法具有更高的肿瘤消融效率、更低的治疗剂量需求以及更少的副作用。然而，PDT/PTT的治疗效率仍受限于实体肿瘤内由异常血管生成和癌细胞代谢改变导致的低氧水平。为应对这些挑战，我们开发了具有高催化活性的多功能纳米颗粒，可将肿瘤过氧化氢（HO）转化为氧气（O）。使用聚（苯乙烯-马来酸酐）（PSMA）作为交联剂，我们制备了致密、高荧光的量子点，使用聚[2,6 -（4,4 - 双（2 - 乙基己基）- 4 - 环戊[2,1 - ;3,4 - ']二噻吩）- 4,7 -（2,1,3 - 苯并噻二唑）]（PCPDTBT）作为用于光动力和光热应用的近红外光敏剂，并掺入锰（Mn）离子以催化HO向O的转化。这些锰掺杂量子点显著增强了氧气生成，在添加HO的情况下将氧气量子产率从0.46提高到0.64，实现了提高PDT效率的目标。通过这种合理设计，我们制备了具有增强的HO向O转化能力的量子点，可用于PDT。对于光热应用，我们的量子点产生的光热转换效率为53%。使用人MCF7腺癌细胞的研究证实了这些量子点在无激光照射时的生物相容性，以及在激光照射下协同PDT/PTT时具有显著的细胞杀伤作用。这些结果突出了量子点在克服氧气限制、平衡PDT/PTT性能以及增强PDT/PTT对癌细胞治疗效果方面的前景。
