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血小板膜仿生纳米粒用于靶向抗肿瘤药物递送。

Platelet-membrane-biomimetic nanoparticles for targeted antitumor drug delivery.

机构信息

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, China.

College of Basic Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, 650500, China.

出版信息

J Nanobiotechnology. 2019 May 13;17(1):60. doi: 10.1186/s12951-019-0494-y.

Abstract

BACKGROUND

Nanoscale drug-delivery systems (DDSs) have great promise in tumor diagnosis and treatment. Platelet membrane (PLTM) biomimetic DDSs are expected to enhance retention in vivo and escape uptake by macrophages, as well as minimizing immunogenicity, attributing to the CD47 protein in PLTM sends "don't eat me" signals to macrophages. In addition, P-selectin is overexpressed on the PLTM, which would allow a PLTM-biomimetic DDS to specifically bind to the CD44 receptors upregulated on the surface of cancer cells.

RESULTS

In this study, porous nanoparticles loaded with the anti-cancer drug bufalin (Bu) were prepared from a chitosan oligosaccharide (CS)-poly(lactic-co-glycolic acid) (PLGA) copolymer. These were subsequently coated with platelet membrane (PLTM) to form PLTM-CS-pPLGA/Bu NPs. The PLTM-CS-pPLGA/Bu NPs bear a particle size of ~ 192 nm, and present the same surface proteins as the PLTM. Confocal microscopy and flow cytometry results revealed a greater uptake of PLTM-CS-pPLGA/Bu NPs than uncoated CS-pPLGA/Bu NPs, as a result of the targeted binding of P-selectin on the surface of the PLTM to the CD44 receptors of H22 hepatoma cells. In vivo biodistribution studies in H22-tumor carrying mice revealed that the PLTM-CS-pPLGA NPs accumulated in the tumor, because of a combination of active targeting effect and the EPR effect. The PLTM-CS-pPLGA/Bu NPs led to more effective tumor growth inhibition over other bufalin formulations.

CONCLUSIONS

Platelet membrane biomimetic nanoparticles played a promising targeted treatment of cancer with low side effect.

摘要

背景

纳米药物递送系统(DDS)在肿瘤诊断和治疗方面具有巨大的应用潜力。血小板膜(PLTM)仿生 DDS 有望增强体内保留和逃避巨噬细胞摄取,同时最小化免疫原性,这归因于 PLTM 中的 CD47 蛋白向巨噬细胞发出“不要吃我”的信号。此外,PLTM 上过度表达 P-选择素,这使得 PLTM 仿生 DDS 能够特异性结合癌细胞表面上调的 CD44 受体。

结果

在这项研究中,从壳聚糖低聚糖(CS)-聚乳酸-羟基乙酸共聚物(PLGA)共聚物中制备了负载抗癌药物蟾毒灵(Bu)的多孔纳米粒子。随后将其用血小板膜(PLTM)包被,形成 PLTM-CS-pPLGA/Bu NPs。PLTM-CS-pPLGA/Bu NPs 的粒径约为 192nm,并具有与 PLTM 相同的表面蛋白。共聚焦显微镜和流式细胞术结果表明,由于 PLTM 表面的 P-选择素与 H22 肝癌细胞的 CD44 受体的靶向结合,PLTM-CS-pPLGA/Bu NPs 的摄取量大于未包被的 CS-pPLGA/Bu NPs。在荷 H22 肿瘤小鼠体内的生物分布研究中,由于主动靶向作用和 EPR 效应的结合,PLTM-CS-pPLGA NPs 在肿瘤中积累。PLTM-CS-pPLGA/Bu NPs 导致比其他蟾毒灵制剂更有效的肿瘤生长抑制。

结论

血小板膜仿生纳米颗粒在低副作用的情况下对癌症具有有前途的靶向治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c8b/6513513/60dac2438b79/12951_2019_494_Sch1_HTML.jpg

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