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用于恶性黑色素瘤靶向治疗的仿生纳米颗粒

Bio-Mimicking Nanoparticles for Targeted Therapy of Malignant Melanoma.

作者信息

Zhou Xu, Yu Ruilian, Cao Xi, Zhang Zhi-Rong, Deng Li

出版信息

J Biomed Nanotechnol. 2019 May 1;15(5):993-1004. doi: 10.1166/jbn.2019.2739.

Abstract

Polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles coated with neutrophil membranes were fabricated to afford a bio-mimicking delivery system and achieve targeted delivery of chemotherapeutics towards malignant melanoma via systemic administration. Using celastrol as the model compound, celastrol-loaded PEG-PLGA nanoparticles coated with neutrophil membranes displayed significantly enhanced cytotoxicity and apoptosis rate in a murine melanoma cell line B16F10 compared to celastrol-loaded PEG-PLGA nanoparticles. Moreover, PEG-PLGA nanoparticles coated with neutrophil membranes exhibited significantly higher internalization efficiency in B16F10 cells than nanoparticles without membrane coating. Next, a B16F10 tumor xenograft mice model was established to explore the biodistribution profiles of PEG-PLGA nanoparticles coated with neutrophil membranes which showed remarkably prolonged blood circulation and more selective accumulation at the tumor site. Celastrol-loaded PEG-PLGA nanoparticles coated with neutrophil membranes also demonstrated greatly improved antitumor efficacy in B16F10 tumor bearing mice xenografts. Taken together, PEG-PLGA nanoparticles coated with neutrophil membranes represent a highly promising nanoscale delivery system to achieve tumor-targeted therapy following systemic administration.

摘要

制备了包被中性粒细胞膜的聚乙二醇-聚乳酸-羟基乙酸共聚物(PEG-PLGA)纳米颗粒,以构建一种仿生递送系统,并通过全身给药实现化疗药物对恶性黑色素瘤的靶向递送。以雷公藤红素作为模型化合物,与负载雷公藤红素的PEG-PLGA纳米颗粒相比,包被中性粒细胞膜的负载雷公藤红素的PEG-PLGA纳米颗粒在小鼠黑色素瘤细胞系B16F10中表现出显著增强的细胞毒性和凋亡率。此外,包被中性粒细胞膜的PEG-PLGA纳米颗粒在B16F10细胞中的内化效率显著高于未包被膜的纳米颗粒。接下来,建立了B16F10肿瘤异种移植小鼠模型,以探究包被中性粒细胞膜的PEG-PLGA纳米颗粒的生物分布情况,结果显示其血液循环显著延长,且在肿瘤部位的选择性积累更多。包被中性粒细胞膜的负载雷公藤红素的PEG-PLGA纳米颗粒在携带B16F10肿瘤的小鼠异种移植瘤中也表现出大大提高的抗肿瘤疗效。综上所述,包被中性粒细胞膜的PEG-PLGA纳米颗粒是一种非常有前景的纳米级递送系统,可在全身给药后实现肿瘤靶向治疗。

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