Hu Mei, Dong Xiaochun, Zhao Weili
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai, 201203, China.
Eur J Med Chem. 2025 Nov 5;297:117934. doi: 10.1016/j.ejmech.2025.117934. Epub 2025 Jul 5.
The aggregation-induced decrease in photosensitization activity is one of the major challenges limiting the clinical application of photosensitizers (PSs). Thus, developing highly efficient PSs for anti-cancer photodynamic therapy (PDT) remains an urgent need. To address this challenge, we designed and synthesized a novel family of efficient aza-BODIPY PSs by inhibiting aggregation with a boron-modified strategy. These novel aza-BODIPY PSs demonstrated significantly enhanced in vitro photodynamic efficacy. Of particular note was derivative A1, which emerged as a highly promising NIR PS with high singlet oxygen yield (rel.rate = 1.79) that obviously superior to the reported compound BDP 4 (rel.rate = 1.23) in PBS. Additionally, A1 showed exceptional cytotoxicity against various cells (IC > 4.5 nM) at a low light dose of 21.6 J/cm. In vivo anti-tumor experiments showed that significant tumor growth suppression following intravenous administration of A1 (2 mg/kg) and subsequent irradiation (21.6 J/cm, λ = 660 nm), outperforming well-known PSs such as ADPM06 and Ce6. Both in vitro and in vivo studies revealed that A1 exhibited an excellent PDT effect at remarkable low drug and light doses.
聚集诱导的光敏活性降低是限制光敏剂（PSs）临床应用的主要挑战之一。因此，开发用于抗癌光动力疗法（PDT）的高效PSs仍然是迫切需求。为应对这一挑战，我们通过硼修饰策略抑制聚集，设计并合成了一类新型高效氮杂硼二吡咯PSs。这些新型氮杂硼二吡咯PSs在体外光动力疗效方面表现出显著增强。特别值得注意的是衍生物A1，它是一种极具潜力的近红外PS，单线态氧产率高（相对速率 = 1.79），在磷酸盐缓冲盐溶液（PBS）中明显优于已报道的化合物BDP 4（相对速率 = 1.23）。此外，在低光剂量21.6 J/cm²下，A1对各种细胞表现出优异的细胞毒性（IC > 4.5 nM）。体内抗肿瘤实验表明，静脉注射A1（2 mg/kg）并随后照射（21.6 J/cm²，λ = 660 nm）后，肿瘤生长受到显著抑制，优于ADPM06和Ce6等知名PSs。体外和体内研究均表明，A1在极低的药物和光剂量下表现出优异的光动力治疗效果。
