文献：Near-infrared light activation of quenched liposomal Ce6 for synergistic cancer

phototherapy with effective skin protection

文献链接：https://www.cqvip.com/doc/journal/2728379199

作者：L Feng，D Tao，Z Dong，Q Chen，Y Chao，Z Liu，M Chen

相关产品：DPPC 二棕榈酸磷脂酰胆碱

原文摘要：Current photodynamic therapy (PDT) is suffering from limited efficacy towards hypoxia tumors and severe post-treatment photo-toxicity such as light-induced skin damages. To make PDT more effective in cancer treatment while being patient-comfortable, herein, a hexylamine conjugated chlorin e6 (hCe6) as the photosensitizer together with a lipophilic near-infrared (NIR) dye 1,1'-dioctadecyl-3,3,3',3'-tetra-methylindotricarbocyanine iodide (DiR) are co-encapsulated into polyethylene glycol (PEG) shelled liposomes. In the obtained DiR-hCe6-liposome, the photosensitizing effect of hCe6 is quenched by DiR via fluorescence resonance energy transfer (FRET). Interestingly, upon irradiation with a 785-nm NIR laser to photobleach DiR, both fluorescence and photodynamic effect of hCe6 in DiR-hCe6-liposome would be activated. Meanwhile, such NIR irradiation applied on tumors of mice with intravenous injection of DiR-hCe6-liposome could result in mild photothermal heating, which in turn would promote intra-tumor blood flow and relieve tumor hypoxia, contributing to the enhanced photodynamic tumor treatment. Importantly, compared to hCe6-loaded liposomes, DiR-hCe6-liposome without being activated by the 785-nm laser shows much lower skin photo-toxicity, demonstrating its great skin protection effect. This work demonstrates a promising yet simple strategy to prepare NIR-light-activatable photodynamic theranostics for synergistic cancer phototherapy, which is featured high specificity/efficacy in tumor treatment with minimal photo-toxicity towards the skin. (C) 2016 Published by Elsevier Ltd.

本文献研究了 DPPC 在近红外光激活淬灭脂质体 Ce6 用于协同cancer中的作用。研究发现，DPPC 可以:提高脂质体 Ce6 的近红外光激活效率，增强其在cancer中的协同作用，并有效减少损伤。本文献设计了一种基于脂质体的近红外光激活系统，其中脂质体 Ce6 作为光敏剂，DPPC 作为稳定剂和增效剂。

图1：dir-hce6-脂质体的化学成分及应用

通过一系列实验，评估了 DPPC 对脂质体 Ce6 性能的影响。结果表明，DPPC 的存在可以提高脂质体 Ce6 的近红外光激活效率，使其在近红外光照射下产生更多的活性氧物种。此外，DPPC 还可以改善脂质体 Ce6 的稳定性，延长其在体内的循环时间，提高其在tumour部位的积累。

图2：dirr-hce6-脂质体的细胞内内化和细胞有害性。

更重要的是，发现 DPPC 可以有效减少脂质体 Ce6 的损伤。这是因为 DPPC 可以形成一层保护性的膜，降低脂质体 Ce6 对正常细胞的非特异性有害性。同时，DPPC 还可以调节细胞内的信号通路，促进皮肤细胞的修复和再生。为了进一步验证该体系的临床应用前景，进行了体内实验。将小鼠分为不同组，分别给予不同处理。结果显示，近红外光激活脂质体 Ce6+DPPC 处理组的tumour生长明显受到抑制。

结论：DPPC在近红外光激活的淬灭脂质体 Ce6 起到作用。发现 DPPC 能够提高脂质体的稳定性，增强近红外光激活的效率。此外，DPPC 还能降低脂质体的有害性。具体的结论包括 DPPC 可以稳定脂质体，提高 Ce6 的近红外光激活效率。