Department of Drug Sciences, University of Catania, I-95125 Catania, Italy.
Department of Drug Science and Technology, University of Torino, I-10125 Torino, Italy.
Bioorg Chem. 2019 Apr;85:18-22. doi: 10.1016/j.bioorg.2018.12.027. Epub 2018 Dec 20.
Combination of photosensitizers (PS) for photodynamic therapy with NO photodonors (NOPD) is opening intriguing horizons towards new and still underexplored multimodal anticancer and antibacterial treatments not based on "conventional" drugs and entirely controlled by light stimuli. In this contribution, we report an intriguing molecular hybrid based on a BODIPY light-harvesting antenna that acts simultaneously as PS and NOPD upon single photon excitation with the highly biocompatible green light. The presented hybrid offers a combination of superior advantages with respect to the other rare cases reported to date, meeting most of the key criteria for both PSs and NOPDs in the same molecular entity such as: (i) capability to generate O and NO with single photon excitation of biocompatible visible light, (ii) excellent O quantum yield and NO quantum efficiency, (iii) photogeneration of NO independent from the presence of oxygen, (iv) large light harvesting properties in the green region. Furthermore, this compound together with its stable photoproduct, is well tolerated by both normal and cancer cells in the dark and exhibits bimodal photomortality of cancer cells under green light excitation due to the combined action of the cytotoxic O and NO.
将光敏剂 (PS) 与一氧化氮供体 (NOPD) 结合用于光动力疗法，为基于“传统”药物的新型、仍未充分探索的多模态抗癌和抗菌治疗开辟了新的前景，并完全受光刺激控制。在本研究中，我们报道了一种基于 BODIPY 光捕获天线的有趣的分子杂交体，该杂交体在单光子激发下可同时作为 PS 和 NOPD，激发光为高度生物相容的绿光。与迄今为止报道的其他少数情况相比，所提出的杂交体具有卓越的优势，在同一分子实体中满足 PS 和 NOPD 的大多数关键标准，例如：(i) 能够在生物相容性可见光的单光子激发下生成 O 和 NO，(ii) 具有优异的 O 量子产率和 NO 量子效率，(iii) 无需氧气存在即可光生成 NO，(iv) 在绿光区具有大的光捕获特性。此外，该化合物及其稳定的光产物在黑暗中均可被正常细胞和癌细胞良好耐受，并由于细胞毒性 O 和 NO 的联合作用，在绿光激发下表现出癌细胞的双重光致死性。
