文献：

Near-Infrared Light-Triggered Thermosensitive Liposomes Modified with Membrane Peptides for the Local Chemo/Photothermal Therapy of Melanoma

文献链接：

作者：

Xinxin Li, Chunsheng Yang, Yingkai Tao,Xiaoyang Hou, Yanqun Liu, Hong Sang ,Guan Jiang

相关产品：

DSPE-PEG2000（磷脂-聚乙二醇2000）

DSPE-PEG2000-MAL（磷脂-聚乙二醇2000-马来酰亚胺）

原文摘要：

Purpose: A near-infrared (NIR)-triggered trans-activating transcriptional activator (TAT)- based targeted drug delivery system for the combined chemo/photothermal therapy of melanoma, namely, TAT-TSL-TMZ (temozolomide)/IR820, was developed for the first time.Methods: TAT-TSL-TMZ/IR820 liposomes were synthesized via thin-film dispersion and sonication. IR820 and TMZ were encased in the inner layer and lipid bilayer of the liposomes, respectively.Results: Dynamic light scattering results showed that the liposomes had an average hydrodynamic size of 166.9 nm and a zeta potential of −2.55 mV. The encapsulation rates of TMZ and IR820 were 35.4% and 28.6%, respectively. The heating curve obtained under nearinfrared (NIR) laser irradiation showed that TAT-TSL-TMZ/IR820 liposomes had good photothermal conversion efficiency. The in vitro drug release curve revealed that NIR laser irradiation could accelerate drug release from TAT-TSL-TMZ/IR820 liposomes. The results of inverted fluorescence microscopy and flow cytometry proved that the uptake of TAT-TSLTMZ/IR820 liposomes by human melanoma cells (MV3 cells) was concentration-dependent and that the liposomes modified with membrane peptides were more likely to be ingested by cells than unmodified liposomes. Confocal laser scanning microscopy indicated that TATTSL-TMZ/IR820 liposomes entered MV3 cells via endocytosis and was stored in lysosomes. In addition, TAT-TSL-TMZ/IR820 liposomes exposed to NIR laser showed 89.73% reduction in cell viability.Conclusion: This study investigated the photothermal conversion, cell uptake, colocation and chemo/photothermal effect of TAT-TSL-TMZ/IR820 liposomes.

DSPE：二硬脂酰磷脂酰乙醇胺，是一种饱和的18碳磷脂，常用于脂质体的合成，具有良好的生物相容性和细胞膜穿透性。PEG：聚乙二醇，是一种亲水性聚合物，分子量在此为2000道尔顿。PEG的引入增加了分子的水溶性，减少了蛋白质的吸附，从而延长了化合物或其他生物活性物质在体内的循环时间。MAL：马来酰亚胺，是一种官能团，通常与巯基（-SH）反应，形成稳定的共价键。这使得DSPE-PEG2000-MAL能够与其他分子或化合物中的巯基反应，实现分子的连接或修饰。基于DSPE-PEG2000-MAL的性质，该文献产品合成流程如下：

图：脂质体合成示意图

DSPE-PEG2000-TAT的合成：

DSPE-PEG2000-Mal和Cys-TAT在水中反应，在室温下温和搅拌。然后用膜对去离子水透析。然后将该产品进行冻干以供进一步使用。利用红外光谱仪对DSPE-PEG2000-TAT脂质体的红外光谱进行了表征和分析。收集适量的TAT、DSPE-PEG2000-Mal和DSPE-PEG2000-TAT脂质体用于溴化钾片剂试验。

TATTSL-TMZ/IR820脂质体的制备：

DPPC、胆固醇、DSPE-PEG2000和DSPE-PEG2000 -TAT的制备以一定的质量比制备脂质体。脂质体被动负载TMZ和IR820用于Treatment 。将 TMZ和IR820以及脂质混合物溶解在甲醇和氯仿中，并在圆底烧瓶中干燥，形成均匀的脂质膜。然后加入适量的PBS，超声水化形成均匀悬浮液。然后用超声细胞破碎仪对脂质体进行超声处理，用高速冷冻离心机离心，以去除未封装的化合物和游离脂质。悬浮沉淀与PBS混合，然后通过聚醚砜过滤器。最终获得最终的TATTSL-TMZ/IR820脂质体溶液，并保存在冰箱中。TSL-TMZ/IR820脂质体的制备步骤相同，但DSPE-PEG2000-TAT脂质体被排除在制备过程之外。

图：显微镜下图像

结论：

该文献成功制备出了基于DSPE-PEG2000-Mal合成的DSPE-PEG2000-TAT、TAT-TSL-TMZ/IR820脂质体。文献对该脂质体的光热转化、细胞摄取、相对位置定位和化学/光热效应等都进行了研究，数据表明实验都取得了良好的结果。