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工程化凋亡体通过血脑屏障搭便车,实现了对脑胶质瘤的光热-化疗联合治疗效果。

Engineered apoptotic bodies hitchhiking across the blood-brain barrier achieved a combined photothermal-chemotherapeutic effect against glioma.

机构信息

Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P.R. China.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, P. R. China.

出版信息

Theranostics. 2023 May 15;13(9):2966-2978. doi: 10.7150/thno.80632. eCollection 2023.

Abstract

Glioma as a highly lethal tumor is difficult to treat since the blood-brain barrier (BBB) restricts drug delivery into the brain. It remains a huge need for developing strategies allowing drug passage across the BBB with high efficacy. Herein, we engineered drug-loaded apoptotic bodies (Abs) loaded with doxorubicin (Dox) and indocyanine green (ICG) to cross the BBB for the treatment of glioma. The confocal laser scanning microscopy was used to characterize the structure and evaluate the hitchhiking effect of the Abs. The BBB-crossing ability and photothermal-chemotherapeutic effect of the drug-loaded Abs were investigated in mice orthotopic glioma model. Engineered Abs loaded with Dox and ICG were successfully prepared. The Abs were phagocytized by macrophages, actively penetrate the BBB and utilizing the hitchhiking effect. The whole process was visualized by near-infrared fluorescence signal with a signal-to-background ratio of 7 in a mouse model of orthotopic glioma. The engineered Abs achieved a combined photothermal-chemotherapeutic effect, leading to a median survival time of 33 days in glioma-bearing mice compared to 22 days in the control group. This study presents engineered drug carriers with the ability to hitchhike across the BBB, providing new opportunities for the treatment of glioma.

摘要

神经胶质瘤是一种高度致命的肿瘤,由于血脑屏障(BBB)限制了药物进入大脑,因此难以治疗。开发能够高效穿透 BBB 的药物传递策略仍然是一个巨大的需求。在此,我们设计了载有阿霉素(Dox)和吲哚菁绿(ICG)的载药凋亡小体(Abs),以穿越 BBB 治疗神经胶质瘤。共聚焦激光扫描显微镜用于表征 Abs 的结构和评估其搭乘效应。在小鼠原位神经胶质瘤模型中研究了载药 Abs 的 BBB 穿透能力和光热化疗效果。成功制备了载有 Dox 和 ICG 的 Abs。Abs 被巨噬细胞吞噬,主动穿透 BBB 并利用搭乘效应。整个过程通过近红外荧光信号可视化,在原位神经胶质瘤小鼠模型中信号与背景的比值为 7。工程化的 Abs 实现了光热化疗的联合效应,使荷瘤小鼠的中位生存时间从对照组的 22 天延长至 33 天。本研究提出了具有穿透 BBB 能力的工程化药物载体,为神经胶质瘤的治疗提供了新的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/327a/10240828/1d54262e1fa3/thnov13p2966g001.jpg

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