Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences, Laboratory for Inorganic Chemical Biology, 75005, Paris, France.
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Angew Chem Int Ed Engl. 2019 Oct 1;58(40):14334-14340. doi: 10.1002/anie.201907856. Epub 2019 Aug 30.
The use of photodynamic therapy (PDT) to treat cancer has received increasing attention over the last years. However, the clinically used photosensitisers (PSs) have some limitations that include poor aqueous solubility, hepatotoxicity, photobleaching, aggregation, and slow clearance from the body, so the design of new classes of PSs is of great interest. We present the use of bis(dipyrrinato)zinc(II) complexes with exceptionally long lifetimes as efficient PDT PSs. Based on the heavy-atom effect, intersystem crossing of these complexes changes the excited state from singlet to a triplet state, thereby enabling singlet oxygen generation. To overcome the limitation of quenching effects in water and improve water solubility, the lead compound 3 was encapsulated in a polymer matrix. It showed impressive phototoxicity upon irradiation at 500 nm in various monolayer cancer cells as well as 3D multicellular tumour spheroids, without observed dark toxicity.
近年来，光动力疗法（PDT）在癌症治疗中的应用受到了越来越多的关注。然而，临床应用的光敏剂（PS）存在一些局限性，包括水溶性差、肝毒性、光漂白、聚集和从体内清除缓慢，因此设计新的 PS 类药物具有重要意义。我们提出使用具有超长寿命的双二吡咯并吡嗪锌（II）配合物作为有效的 PDT PS。基于重原子效应，这些配合物的系间窜越将激发态从单重态转变为三重态，从而能够产生单线态氧。为了克服在水中的猝灭效应的限制并提高水溶性，将铅化合物 3 封装在聚合物基质中。在 500nm 照射下，它在各种单层癌细胞和 3D 多细胞肿瘤球体中表现出令人印象深刻的光毒性，而没有观察到暗毒性。
