Single-atom replacement as a general approach towards visible-light/near-infrared heavy-atom-free photosensitizers for photodynamic therapy.,Chemical Science

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Single-atom replacement as a general approach towards visible-light/near-infrared heavy-atom-free photosensitizers for photodynamic therapy.
Chemical Science ( IF 7.6 ) Pub Date : 2020-06-02 , DOI: 10.1039/d0sc02286a
Juan Tang ₁ , Lushun Wang ₁ , Axel Loredo ₁ , Carson Cole ₁ , Han Xiao _{1,

2,

3}

Affiliation

Photodynamic therapy has become an emerging strategy for the treatment of cancer. This technology relies on the development of photosensitizers (PSs) that convert molecular oxygen to cytotoxic reactive oxygen species upon exposure to light. In this study, we have developed a facile and general strategy for obtaining visible light/near-infrared-absorbing PSs by performing a simple sulfur-for-oxygen replacement within existing fluorophores. Thionation of carbonyl groups within existing fluorophore cores leads to an improvement of the singlet oxygen quantum yield and molar absorption coefficient at longer wavelengths (deep to 600–800 nm). Additionally, these thio-based PSs lack dark cytotoxicity but exhibit significant phototoxicity against monolayer cancer cells and 3D multicellular tumor spheroids with IC₅₀ in the micromolar range. To achieve tumor-specific delivery, we have conjugated these thio-based PSs to an antibody and demonstrated their tumor-specific therapeutic activity.

中文翻译：

单原子替代作为光动力疗法中可见光/近红外无重原子光敏剂的一般方法。

光动力疗法已成为治疗癌症的新兴策略。该技术依赖于光敏剂（PS）的开发，光敏剂在暴露于光时将分子氧转化为细胞毒性活性氧。在这项研究中，我们开发了一种简单且通用的策略，通过在现有荧光团内进行简单的硫对氧替换来获得可见光/近红外吸收 PS。现有荧光团核心内的羰基的硫化可提高较长波长（深至 600–800 nm）的单线态氧量子产率和摩尔吸收系数。此外，这些硫基 PS 缺乏暗细胞毒性，但对单层癌细胞和 3D 多细胞肿瘤球体表现出显着的光毒性，IC ₅₀在微摩尔范围内。为了实现肿瘤特异性递送，我们将这些硫基 PS 与抗体结合，并证明了它们的肿瘤特异性治疗活性。

更新日期：2020-07-08

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