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用于黑色素瘤局部化疗/光热治疗的膜肽修饰近红外光触发热敏脂质体

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

作者信息

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

机构信息

Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, 221004, People's Republic of China.

Department of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Feb 25;14:1317-1329. doi: 10.2147/OTT.S287272. eCollection 2021.

Abstract

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 near-infrared (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-TSL-TMZ/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 TAT-TSL-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.

摘要

目的

首次开发了一种基于近红外(NIR)触发的反式激活转录激活因子(TAT)的靶向药物递送系统,用于黑色素瘤的联合化疗/光热治疗,即TAT-TSL-替莫唑胺(TMZ)/IR820。

方法

通过薄膜分散和超声处理合成TAT-TSL-TMZ/IR820脂质体。IR820和TMZ分别包裹在脂质体的内层和脂质双层中。

结果

动态光散射结果表明,脂质体的平均流体动力学尺寸为166.9nm,ζ电位为-2.55mV。TMZ和IR820的包封率分别为35.4%和28.6%。在近红外(NIR)激光照射下获得的加热曲线表明,TAT-TSL-TMZ/IR820脂质体具有良好的光热转换效率。体外药物释放曲线显示,NIR激光照射可加速药物从TAT-TSL-TMZ/IR820脂质体中释放。倒置荧光显微镜和流式细胞术结果证明,人黑色素瘤细胞(MV3细胞)对TAT-TSL-TMZ/IR820脂质体的摄取具有浓度依赖性,并且与未修饰的脂质体相比,用膜肽修饰的脂质体更易被细胞摄取。共聚焦激光扫描显微镜表明,TAT-TSL-TMZ/IR820脂质体通过内吞作用进入MV3细胞并储存在溶酶体中。此外,暴露于NIR激光的TAT-TSL-TMZ/IR820脂质体使细胞活力降低了89.73%。

结论

本研究考察了TAT-TSL-TMZ/IR820脂质体的光热转换、细胞摄取、共定位及化疗/光热效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b244/7920603/a59f6ca35d47/OTT-14-1317-g0001.jpg

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