IBMM, Université de Montpellier, CNRS, ENSCM, Montpellier, France.
CNRS, LCC (Laboratoire de Chimie de Coordination, UPR8241), Université de Toulouse, 205 route de Narbonne, F-31077 Toulouse, France.
Int J Pharm. 2019 Oct 5;569:118585. doi: 10.1016/j.ijpharm.2019.118585. Epub 2019 Jul 31.
In this work, we implemented a supramolecular approach in order to combine photodynamic therapy (PDT) with gene therapy. We made use of a simple cationic guanidylated porphyrin (H‑PG) with the hypothesis that porphyrin aggregates should be capable of complexing siRNA through multivalent interactions and thus contribute to its intracellular delivery, while remaining active photosensitizers for PDT. The PDT effect of H‑PG was shown by incubating human breast cancer cells (MDA-MB-231) with H‑PG followed by light-irradiation at 405 nm. On the other hand, while siRNA do not enter cells alone, we showed, by fluorescence confocal microscopy and flow cytometry, that H‑PG promotes the internalization of Atto-488 siRNA. Finally, studying the combined PDT and delivery of siRNA directed against inhibitory apoptotic protein (IAP) family, we found an additive effect of the two therapies, thereby demonstrating that H‑PG is capable of acting both as a photosensitizer and supramolecular siRNA vector.
在这项工作中，我们采用了一种超分子方法，将光动力疗法（PDT）与基因治疗相结合。我们利用了一种简单的阳离子胍基化卟啉（H-PG），假设卟啉聚集体能够通过多价相互作用与 siRNA 复合，从而有助于其细胞内递呈，同时仍然是 PDT 的活性光敏剂。通过用 405nm 的光照射孵育有人乳腺癌细胞（MDA-MB-231）的 H-PG，证明了 H-PG 的 PDT 效应。另一方面，由于 siRNA 不能单独进入细胞，我们通过荧光共聚焦显微镜和流式细胞术表明，H-PG 促进了 Atto-488 siRNA 的内化。最后，研究针对抑制凋亡蛋白（IAP）家族的 siRNA 的联合 PDT 和递送，我们发现两种疗法具有相加效应，从而证明 H-PG 能够同时作为光敏剂和超分子 siRNA 载体发挥作用。
