光动力疗法 (PDT) 是一种临床批准的癌症治疗方法，基于产生细胞毒性活性氧来诱导细胞死亡。然而，其效率取决于光敏剂（PS）的分布和光穿透组织的深度。病理性癌症组织的 pH 值往往低于健康组织，这启发我们探索基于可调谐近红外 (NIR) 硼二吡咯亚甲基 (BODIPY) 染料的双靶向 pH 激活光敏剂。我们的 BODIPY PS 被设计为具有三个主要属性：(i) 生物素或 cRGD 肽作为有效的癌细胞靶向单元，(ii) 在酸性（pH <6.5）条件下质子化的氨基部分，用于 pH 激活 PS 基光诱导电子转移 (PET) 和 (iii) 亲水基团增强疏水性 BODIPY 染料的水溶性。与健康的 MRC-5（生物素阴性）细胞相比，用合适的光（> 640 nm）照射此类化合物可对 HeLa（αvβ3 整合素和生物素受体阳性）和 A549（生物素受体阳性）细胞产生高光毒性。此外，在选定的细胞系 (>10 μM) 上未观察到暗毒性，为肿瘤靶向光动力疗法提供了有前景的光敏剂。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Photodynamic therapy (PDT) is a clinically-approved cancer treatment that is based on production of cytotoxic reactive oxygen species to induce cell death. However, its efficiency depends on distribution of photosensitizer (PS) and depth of light penetration through the tissues. Tendency of pathological cancer tissues to exhibit lower pH than healthy tissues inspired us to explore dual-targeted pH-activatable photosensitizers based on tunable near-infrared (NIR) boron-dipyrromethene (BODIPY) dyes. Our BODIPY PSs were designed to carry three main attributes: (i) biotin or cRGD peptide as an effective cancer cell targeting unit, (ii) amino moiety that is protonated in acidic (pH <6.5) conditions for pH-activation of the PS based on photoinduced electron transfer (PET) and (iii) hydrophilic groups enhancing the water solubility of very hydrophobic BODIPY dyes. Illumination of such compounds with suitable light (>640nm) allowed for high phototoxicity against HeLa (αvβ3 integrin and biotin receptor positive) and A549 (biotin receptor positive) cells compared to healthy MRC-5 (biotin negative) cells. Moreover, no dark toxicity was observed on selected cell lines (>10 μM) providing promising photosensitizers for tumour-targeted photodynamic therapy.Copyright © 2024 Elsevier B.V. All rights reserved.