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用于治疗神经胶质瘤的双靶点肽修饰红细胞膜包被聚乳酸-羟基乙酸共聚物纳米粒

Dual-Target Peptide-Modified Erythrocyte Membrane-Enveloped PLGA Nanoparticles for the Treatment of Glioma.

作者信息

Cui Yuexin, Sun Jiejie, Hao Wenyan, Chen Mengyu, Wang Yingzi, Xu Fenghua, Gao Chunsheng

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China.

出版信息

Front Oncol. 2020 Oct 21;10:563938. doi: 10.3389/fonc.2020.563938. eCollection 2020.

Abstract

Penetration of the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB) remains a significant challenge for the delivery of drugs in the treatment of glioma. Therefore, the development of targeted preparations with the ability to penetrate the BBB and BBTB, and target gliomas, is an important approach if we are to improve the efficacy of glioma treatment. In the current study, an active targeting preparation based on PLGA nanoparticles coated with erythrocyte membranes (RBCNPs) and dual-modified with WSW and NGR peptide ligands (WSW/NGR-RBCNPs). Euphorbia factor L1 (EFL1) extracted from euphorbiae semen was used as the model drug. The final nanoparticles were characterized by and tests. results showed that EFL1-loaded WSW/NGR-RBCNPs were taken up by cells and had the ability to penetrate the BBB and BBTB and produce cytotoxic effects. Furthermore, studies in mice showed that when injected intravenously, these specialized NPs could enter the brain, target tumor tissue, and significantly extend life span. The results showed that dual-targeting EFL1-loaded WSW/NGR-RBCNPs have significant potential as a nanotherapeutic tool for the treatment of brain glioma.

摘要

血脑屏障(BBB)和血脑肿瘤屏障(BBTB)的穿透对于胶质瘤治疗中药物的递送仍然是一项重大挑战。因此,如果我们要提高胶质瘤的治疗效果,开发具有穿透BBB和BBTB并靶向胶质瘤能力的靶向制剂是一种重要方法。在本研究中,一种基于聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒的主动靶向制剂,该纳米颗粒包被有红细胞膜(RBCNPs),并用WSW和NGR肽配体进行双重修饰(WSW/NGR-RBCNPs)。从千金子中提取的千金子素L1(EFL1)用作模型药物。最终的纳米颗粒通过 和 测试进行表征。 结果表明,负载EFL1的WSW/NGR-RBCNPs被细胞摄取,具有穿透BBB和BBTB并产生细胞毒性作用的能力。此外,在小鼠中的 研究表明,静脉注射时,这些特殊的纳米颗粒可以进入大脑,靶向肿瘤组织,并显著延长生存期。结果表明,负载EFL1的双靶向WSW/NGR-RBCNPs作为治疗脑胶质瘤的纳米治疗工具具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64bf/7609867/dc3842126cfc/fonc-10-563938-g001.jpg

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