Department of Biochemistry, Simmons Comprehensive Cancer Center , The University of Texas Southwestern Medical Center , Dallas , Texas 75390 , United States.
ACS Appl Mater Interfaces. 2018 May 16;10(19):16335-16343. doi: 10.1021/acsami.8b04710. Epub 2018 May 3.
Current photosensitizers (PSs) for photodynamic therapy (PDT) are limited by their low water solubility and tendency to aggregate, low near-infrared (NIR) absorption, and low cancer selectivity. Here, we designed iodinated, water-soluble NIR boron dipyrromethene-based PSs to achieve image-guided and efficient PDT against cancer in vivo that is enhanced by leveraging tumor-specific pH-responsive activation. PEG2k5c-I and PEG2k5c-OMe-I localized to tumors and were activated by acidic pH in the tumor microenvironment to produce O and fluorescence for efficient PDT and effective cancer detection after intravenous administration. Upon NIR irradiation, these PSs exhibited strong NIR absorption at 660 and 690 nm, stable NIR emission at 692 and 742 nm, and high O quantum yields of 0.78 and 0.72 in acidic pH. PEG2k5c-I and PEG2k5c-OMe-I killed cancer cells upon irradiation of NIR light and were nontoxic without irradiation. Light-activated PDT treatment of breast cancer tumors in mice resulted in suppression of tumor growth, DNA damage, and necrosis selectively in tumors. This work thus introduces a versatile method to directly synthesize modular pH-responsive water-soluble PSs and provides a versatile strategy for activatable PDT against cancer.
目前的光动力疗法（PDT）光敏剂（PS）受到水溶性差、容易聚集、近红外（NIR）吸收低、对癌症选择性低等限制。在这里，我们设计了碘代、水溶性 NIR 硼二吡咯甲川类 PS，以实现体内图像引导和高效 PDT 治疗癌症，并通过利用肿瘤特异性 pH 响应性激活来增强治疗效果。PEG2k5c-I 和 PEG2k5c-OMe-I 定位于肿瘤部位，并在肿瘤微环境的酸性 pH 下被激活，以产生 O 和荧光，从而实现高效 PDT，并在静脉给药后有效检测癌症。在近红外光照射下，这些 PS 在 660nm 和 690nm 处表现出强的近红外吸收，在 692nm 和 742nm 处有稳定的近红外发射，并且在酸性 pH 下具有 0.78 和 0.72 的高 O 量子产率。PEG2k5c-I 和 PEG2k5c-OMe-I 在近红外光照射下杀死癌细胞，并且在没有光照的情况下没有毒性。在小鼠乳腺癌肿瘤的光激活 PDT 治疗中，肿瘤生长受到抑制，肿瘤内的 DNA 损伤和坏死具有选择性。这项工作因此引入了一种直接合成模块化 pH 响应性水溶性 PS 的通用方法，并为针对癌症的可激活 PDT 提供了一种通用策略。
