Conventional photosensitizers (PSs) used in photodynamic therapy (PDT) have shown preliminary success; however, they are often associated with several limitations including potential dark toxicity in healthy tissues, limited efficacy under acidic and hypoxic conditions, suboptimal fluorescence imaging capabilities, and nonspecific targeting during treatment. In response to these challenges, we developed a heavy-atom-free PS, denoted as Cz-SB, by incorporating ethyl carbazole into a thiophene-fused BODIPY core. A comprehensive investigation into the photophysical properties of Cz-SB was conducted through a synergistic approach involving experimental and computational investigations. The enhancement of intersystem crossing (k_ISC) and fluorescence emission (k_fl) rate constants was achieved through a donor–acceptor pair-mediated charge transfer mechanism. Consequently, Cz-SB demonstrated remarkable efficiency in generating reactive oxygen species (ROS) under acidic and low-oxygen conditions, making it particularly effective for hypoxic cancer PDT. Furthermore, Cz-SB exhibited good biocompatibility, fluorescence imaging capabilities, and a high degree of localization within the mitochondria of living cells. We posit that Cz-SB holds substantial prospects as a versatile PS with innovative molecular design, representing a potential “one-for-all” solution in the realm of cancer phototheranostics.

中文翻译：

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无重原子光敏剂的电荷转移促进激发态，用于线粒体靶向荧光成像和缺氧光动力疗法的有效应用

光动力疗法（PDT）中使用的传统光敏剂（PS）已取得初步成功；然而，它们通常存在一些局限性，包括健康组织中潜在的暗毒性、酸性和缺氧条件下的功效有限、荧光成像能力欠佳以及治疗期间的非特异性靶向。为了应对这些挑战，我们通过将乙基咔唑掺入噻吩稠合的 BODIPY 核中，开发了一种不含重原子的 PS，表示为Cz-SB 。通过实验和计算研究的协同方法对Cz-SB的光物理性质进行了全面的研究。通过供体-受体对介导的电荷转移机制实现了系间窜越（ k _ISC）和荧光发射（k _fl ）速率常数的增强。因此，Cz-SB在酸性和低氧条件下表现出显着的产生活性氧 (ROS) 的效率，使其对缺氧癌症 PDT 特别有效。此外，Cz-SB表现出良好的生物相容性、荧光成像能力以及在活细胞线粒体内的高度定位。我们认为Cz-SB作为具有创新分子设计的多功能 PS 具有广阔的前景，代表了癌症光治疗领域潜在的“一劳永逸”解决方案。