Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnels, Institut de Chimie de Strasbourg UMR 7177/CNRS, Université de Strasbourg, 4, rue Blaise Pascal, 67000 Strasbourg, France.
CAMB, UMR 7199, UdS/CNRS, Faculté de Pharmacie, Université de Strasbourg, 74 route du Rhin, 67401 Illkirch, France.
Org Biomol Chem. 2019 Jul 21;17(27):6585-6594. doi: 10.1039/c9ob00731h. Epub 2019 Apr 29.
Despite the advantages of photodynamic therapy (PDT) over chemotherapy or radiotherapy such as low side effects, lack of treatment resistance and spatial selectivity inherent to light activation of the drug, several limitations especially related to the photosensitiser (PS) prevent PDT from becoming widespread in oncology. Herein, new folic acid- and biotin-conjugated PSs for tumour-targeting PDT are reported, with promising properties related to PDT such as intense absorption following one-photon excitation in the red or two-photon excitation in the near-infrared, and also high singlet oxygen quantum yield (close to 70% in DMSO). Cellular studies demonstrated that both targeted PSs induced phototoxicity, the folate-targeted PS being the most effective one with 80% of cell death following 30 min of irradiation and a phototoxicity four times higher than that of the non-targeted PS. This result is in accordance with the uptake of the folate-targeted PS in HeLa cells, mediated by the folate receptors. Moreover, this folate-targeted PS was also phototoxic following two-photon excitation at 920 nm, opening new perspectives for highly selective PDT treatment of small and deep tumours.
尽管光动力疗法（PDT）具有优于化疗或放疗的优势，如副作用低、缺乏治疗耐药性以及药物的光激活固有空间选择性，但由于几个限制因素，特别是与光敏剂（PS）相关的限制因素，PDT 尚未在肿瘤学中广泛应用。本文报道了用于肿瘤靶向 PDT 的新型叶酸和生物素偶联 PS，具有与 PDT 相关的有前景的特性，例如在红光单光子激发或近红外双光子激发下的强烈吸收，以及高光敏化单线态氧量子产率（接近 70%在 DMSO 中）。细胞研究表明，两种靶向 PS 都诱导了光毒性，叶酸靶向 PS 最为有效，在照射 30 分钟后有 80%的细胞死亡，光毒性比非靶向 PS 高四倍。这一结果与叶酸靶向 PS 通过叶酸受体介导在 HeLa 细胞中的摄取一致。此外，这种叶酸靶向 PS 在 920nm 的双光子激发下也具有光毒性，为小而深的肿瘤的高度选择性 PDT 治疗开辟了新的前景。
