Lioret Vivian, Saou Sébastien, Berrou Anne, Lernerman Liana, Arnould Christine, Decréau Richard A
Université de Bourgogne, Dijon, France.
INRAE, Dijon, France.
Photochem Photobiol Sci. 2023 Feb;22(2):303-309. doi: 10.1007/s43630-022-00313-0. Epub 2022 Oct 6.
A poly-cationic theranostic macrocycle was developed to perform confocal microscopy imaging and photodynamic therapy studies on a model of melanoma cancer, one of the most aggressive cancer. Hence, an octa-imidazolium zinc phthalocyanine was conveniently synthesized in large amount in three steps in a 44% overall yield: upon double nucleophilic aromatic substitution, cyclo-tetramerization and quaternization reactions. Such an octa-cationic molecule was readily soluble in physiological media, reaching concentrations beyond 1 mM. It showed fluorescence properties in aqueous medium (Φ = 0.31) with no noticeable aggregation, spectroscopy studies showed. In vitro confocal fluorescence microscopy studies carried out on murine melanoma model (B16F10 cells) showed that the fluorophore was mainly located in the cell nucleolus, an organelle of interest for the treatment of cancer. The anticancer photodynamic potential of the octa-cationic photosensitizer could be measured (IC = 5.4 µM) using the MTS viability assay. Both fluorescence microscopy studies and photodynamic studies demonstrate the octa-cationic molecule is theranostic and could be further developed for future photodynamic diagnosis (PDD) and photodynamic inactivation of micro-organisms (PDI).
开发了一种聚阳离子诊疗大环化合物，用于对黑色素瘤模型进行共聚焦显微镜成像和光动力疗法研究，黑色素瘤是最具侵袭性的癌症之一。因此，通过双亲核芳香取代、环四聚化和季铵化反应，分三步方便地大量合成了八咪唑锌酞菁，总产率为44%。这种八阳离子分子易溶于生理介质，浓度超过1 mM。光谱研究表明，它在水性介质中具有荧光特性（Φ = 0.31），且无明显聚集。对小鼠黑色素瘤模型（B16F10细胞）进行的体外共聚焦荧光显微镜研究表明，荧光团主要位于细胞核仁，这是治疗癌症的一个重要细胞器。使用MTS活力测定法可测量八阳离子光敏剂的抗癌光动力潜力（IC = 5.4 μM）。荧光显微镜研究和光动力研究均表明，八阳离子分子具有诊疗功能，可进一步开发用于未来的光动力诊断（PDD）和微生物光动力灭活（PDI）。
