研究动态
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光动力治疗方案后,光敏剂的封装会恶化细胞反应,并且聚合物胶束本身可充当生物调节剂。

Encapsulation of photosensitizer worsen cell responses after photodynamic therapy protocol and polymer micelles act as biomodulators on their own.

发表日期:2024 Aug 13
作者: Rachel Brival, Nathan Ghafari, Anne-Françoise Mingotaud, Isabelle Fourquaux, Véronique Gilard, Fabrice Collin, Patricia Vicendo, Stéphane Balayssac, Laure Gibot
来源: INTERNATIONAL JOURNAL OF PHARMACEUTICS

摘要:

光动力疗法(PDT)是一种光化学治疗方式,临床上用于皮肤病学、眼科和肿瘤学应用。 Pheo a 被用作模型光敏剂,无论是游离形式还是封装在聚(环氧乙烷)-嵌段-聚(ε-己内酯)(PEO-PCL)聚合物胶束中。嵌段共聚物胶束是水溶性生物相容性纳米容器,具有输送疏水性药物的巨大潜力。在整个实验过程中还测试了空 PEO-PCL 胶束。目标是对游离和封装的 Pheo a 诱导的人结直肠肿瘤 HCT-116 细胞反应进行体外研究,包括细胞结构、质膜交换、线粒体功能和代谢紊乱。在校准的 PDT 方案中,封装增强了 Pheo a 渗透(流式细胞术、共焦显微镜)和细胞死亡(Prestoblue 测定),导致细胞形态 (SEM) 和细胞骨架组织(共焦)发生巨大变化、线粒体功能障碍和完整性丧失 (TEM) )、穿过质膜的快速且大量的离子通量(ICP-OES、离子色谱)以及代谢改变,包括氨基酸和胆碱衍生物水平的增加(1H NMR)。详细的研究提供了对封装 Pheo-PDT 多方面作用的见解,强调了在理解治疗结果时考虑光敏剂及其递送系统的重要性。该研究还对空纳米载体本身的更广泛影响提出了疑问,并鼓励对其生物效应进行更全面的探索。版权所有 © 2024。由 Elsevier B.V. 出版。
Photodynamic therapy (PDT) is a photochemical therapeutic modality used clinically for dermatological, ophthalmological and oncological applications. Pheo a was used as a model photosensitizer, either in its free form or encapsulated within poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) polymer micelles. Block copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs. Empty PEO-PCL micelles were also tested throughout the experiments. The goal was to conduct an in vitro investigation into human colorectal tumor HCT-116 cellular responses induced by free and encapsulated Pheo a in terms of cell architecture, plasma membrane exchanges, mitochondrial function, and metabolic disturbances. In a calibrated PDT protocol, encapsulation enhanced Pheo a penetration (flow cytometry, confocal microscopy) and cell death (Prestoblue assay), causing massive changes to cell morphology (SEM) and cytoskeleton organization (confocal), mitochondrial dysfunction and loss of integrity (TEM), rapid and massive ion fluxes across the plasma membrane (ICP-OES, ion chromatography), and metabolic alterations, including increased levels of amino acids and choline derivatives (1H NMR). The detailed investigation provides insights into the multifaceted effects of encapsulated Pheo-PDT, emphasizing the importance of considering both the photosensitizer and its delivery system in understanding therapeutic outcomes. The study also raises questions as to the broader impact of empty nanovectors per se, and encourages a more comprehensive exploration of their biological effects.Copyright © 2024. Published by Elsevier B.V.