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聚山梨酯 80 修饰的紫杉醇载 PLGA 纳米粒通过聚焦超声增强抗神经胶质瘤疗效的机制。

Mechanisms of enhanced antiglioma efficacy of polysorbate 80-modified paclitaxel-loaded PLGA nanoparticles by focused ultrasound.

机构信息

Department of Medicine Ultrasonics, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.

出版信息

J Cell Mol Med. 2018 Sep;22(9):4171-4182. doi: 10.1111/jcmm.13695. Epub 2018 Jun 29.

DOI:10.1111/jcmm.13695
PMID:29956460
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6111803/
Abstract

The presence of blood-brain barrier (BBB) greatly limits the availability of drugs and their efficacy against glioma. Focused ultrasound (FUS) can induce transient and local BBB opening for enhanced drug delivery. Here, we developed polysorbate 80-modified paclitaxel-loaded PLGA nanoparticles (PS-80-PTX-NPs, PPNP) and examined the enhanced local delivery into the brain for glioma treatment by combining with FUS. Our result showed PPNP had good stability, fast drug release rate and significant toxicity to glioma cells. Combined with FUS, PPNP showed a stronger BBB permeation efficiency both in the in vitro and in vivo BBB models. Mechanism studies revealed the disrupted tight junction, reduced P-glycoprotein expression and ApoE-dependent PS-80 permeation collectively contribute to the enhanced drug delivery, resulting in significantly stronger antitumour efficacy and longer survival time in the tumour-bearing mice. Our study provided a new strategy to efficiently and locally deliver drugs into the brain to treat glioma.

摘要

血脑屏障（BBB）的存在极大地限制了药物的有效性，使其难以治疗脑胶质瘤。聚焦超声（FUS）可以诱导血脑屏障短暂且局部开放，从而增强药物递送。在这里，我们开发了聚山梨酯 80 修饰的紫杉醇负载 PLGA 纳米粒（PS-80-PTX-NPs，PPNP），并通过结合 FUS 研究了增强局部递送至大脑以治疗脑胶质瘤的效果。我们的结果表明，PPNP 具有良好的稳定性、快速的药物释放率和对神经胶质瘤细胞的显著毒性。与 FUS 联合使用时，PPNP 在体外和体内 BBB 模型中均表现出更强的 BBB 渗透效率。机制研究表明，紧密连接的破坏、P-糖蛋白表达的减少和 ApoE 依赖性 PS-80 渗透共同促进了药物的递送，从而使荷瘤小鼠的抗肿瘤疗效显著增强，存活时间延长。我们的研究为高效、局部递送至大脑以治疗脑胶质瘤提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/befee191fc0e/JCMM-22-4171-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/dbbbf6b5ebd2/JCMM-22-4171-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/349a9e99cc4c/JCMM-22-4171-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/befee191fc0e/JCMM-22-4171-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/63d0d3ade9ea/JCMM-22-4171-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/6607e86dbec6/JCMM-22-4171-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/5835f69e89a3/JCMM-22-4171-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e9d/6111803/befee191fc0e/JCMM-22-4171-g007.jpg

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