The poor selectivity of photosensitizers for tumor tissue remains a drawback in photodynamic therapy (PDT) and could be improved by adapted formulations. The cellular uptake, localization and phototoxicity of meta-tetra(hydroxyphenyl)chlorin (mTHPC) encapsulated in submicronic colloidal carriers have been studied in macrophage-like J774 cells and HT 29 human adenocarcinoma cells. Nanocapsules with an external layer made of poly(D,L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG NCs), PLA coated with poloxamer 188 (polox PLA NCs) and oil/water nanoemulsion (NE) have been examined. The cellular uptake by J774, as determined by microspectroflorimetry, is reduced with mTHPC encapsulated into surface-modified NCs--PLA-PEG and polox PLA--compared with naked PLA, indicating a possible limitation of the clearance of such carriers by the reticuloendothelial system. Encapsulation also modifies the interaction between mTHPC and HT29 cells. Compared with the manufacturer's solution (PEG, ethanol, water), the cellular uptake is strongly reduced. However, the HT29 phototoxicity is much less affected and a protecting effect against plasma proteins is observed. Fluorescence microscopy reveals a specific punctate fluorescence pattern with PLA-PEG and polox PLA NCs in contrast to a more diffuse distribution with NE and solution, indicating that photodamage targeting could be different. These findings suggest that photosensitizers encapsulated into surface-modified nanocapsules could be a promising approach for improving PDT efficacy and this has to be confirmed in vivo.

译文

光敏剂对肿瘤组织的选择性差仍然是光动力疗法 (PDT) 的缺点,并且可以通过调整配方来改善。已在巨噬细胞样J774细胞和HT 29人腺癌细胞中研究了封装在亚微离子胶体载体中的间四 (羟基苯基) 氯蛋白 (mTHPC) 的细胞摄取,定位和光毒性。已经检查了具有由聚 (D,L乳酸) (PLA NCs) 制成的外层的纳米胶囊,接枝聚乙二醇的PLA (PLA-PEG NCs),涂有泊洛沙姆188的PLA (polox PLA NCs) 和油/水纳米乳液 (NE)。与裸露的PLA相比,通过显微分光光度法测定的J774的细胞摄取被封装在表面修饰的NCs (PLA-PEG和polox PLA) 中的mTHPC降低,这表明网状内皮系统可能限制了此类载体的清除。封装也改变了mTHPC和HT29细胞之间的相互作用。与制造商的溶液 (PEG,乙醇,水) 相比,细胞摄取大大减少。然而,HT29光毒性的影响要小得多,并且观察到对血浆蛋白的保护作用。荧光显微镜显示出PLA-PEG和polox PLA NCs具有特定的点状荧光模式,而NE和溶液具有更漫射的分布,表明光损伤靶向可能有所不同。这些发现表明,封装在表面改性的纳米胶囊中的光敏剂可能是改善PDT功效的有前途的方法,这必须在体内得到证实。

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