光敏剂的封装使光动力疗法方案和聚合物胶束后的细胞反应恶化为生物调节剂
Encapsulation of photosensitizer worsen cell responses after photodynamic therapy protocol and polymer micelles act as biomodulators on their own
影响因子:5.20000
发表日期:2024 Sep 30
作者:
Rachel Brival, Nathan Ghafari, Anne-Françoise Mingotaud, Isabelle Fourquaux, Véronique Gilard, Fabrice Collin, Patricia Vicendo, Stéphane Balayssac, Laure Gibot
摘要
光动力疗法（PDT）是一种光化学治疗方式，用于皮肤病学，眼科和肿瘤学应用。 Pheo A以自由形式或封装在聚（乙烷氧化物）-Block-POLY（ε-二苯乙烯）（PEO-PCL）聚合物胶束中的模型光敏剂。块共聚物胶束是水溶性的生物相容性纳米核心因素，具有递送疏水性药物的巨大潜力。在整个实验中，还测试了空的PEO-PCL胶束。目的是在细胞结构，质膜交换，线粒体功能和代谢干扰方面对人结直肠肿瘤HCT-116细胞反应进行体外研究。在校准的PDT方案中，封装增强了PheO A渗透率（流式细胞术，共聚焦显微镜）和细胞死亡（Prestoblue Assay），从而导致细胞形态（SEM）和细胞骨架组织（COMOCOCAL）的细胞形态（SEM）和细胞骨骼组织（共焦），线粒体功能障碍和群体的损失（tembrane flas and tembrane flase and tembrane gropmbrane gropmbrane gropmbr），群体的变化（tem） （ICP-OES，离子色谱）和代谢改变，包括氨基酸和胆碱衍生物的水平升高（1H NMR）。详细的调查提供了对封装的Pheo-PDT的多方面影响的见解，强调了考虑光敏剂及其输送系统在理解治疗结果方面的重要性。这项研究还提出了关于空纳米摩氏原身的更广泛影响的问题，并鼓励对其生物学作用进行更全面的探索。
Abstract
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.