Abstract：
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.
摘要：
光动力疗法(PDT)是临床批准的癌症治疗,其基于细胞毒性活性氧的产生以诱导细胞死亡。然而,其效率取决于光敏剂(PS)的分布和光穿透组织的深度。病理癌组织表现出比健康组织更低的pH的趋势启发我们探索基于可调近红外（NIR）硼-二吡咯亚甲基（BODIPY）染料的双靶向可pH激活的光敏剂。我们的BODIPYPS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位，(ii)基于光诱导电子转移(PET)在用于PS的pH活化的酸性(pH<6.5)条件下质子化的氨基部分,和(iii)增强非常疏水的BODIPY染料的水溶性的亲水基团。与健康的MRC-5(生物素阴性)细胞相比,用合适的光(>640nm)照射此类化合物允许对HeLa(αvβ3整联蛋白和生物素受体阳性)和A549(生物素受体阳性)细胞的高光毒性。此外，在选定的细胞系(>10μM)上没有观察到暗毒性,为肿瘤靶向光动力疗法提供有前景的光敏剂。
