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用于脑胶质瘤精准给药与可视化治疗的靶向给药系统的智能设计

Smart Design of Targeted Drug Delivery System for Precise Drug Delivery and Visual Treatment of Brain Gliomas.

作者信息

Song Baoqin, Wu Mengru, Qin Lijing, Liang Wanjun, Wang Xiu

机构信息

School of Pharmaceutical Sciences and Institute of Materia Medica, Shandong First Medical University and Shandong Academy of Medical Sciences, National Key Laboratory of Advanced Drug Delivery System, Key Laboratory for Biotechnology Drugs of National Health Commission (Shandong Academy of Medical Sciences), Key Lab for Rare and Uncommon Diseases of Shandong Province, Jinan, Shandong, 250117, China.

出版信息

Adv Healthc Mater. 2025 Feb;14(4):e2402967. doi: 10.1002/adhm.202402967. Epub 2024 Dec 20.

Abstract

In the treatment of glioma, which is one of the malignant tumors, although chemotherapy is used as the most common treatment method, it often suffers from low bioavailability. Therefore, improving the precision and efficiency of drugs is crucial in treating gliomas and a great challenge. Here, an advanced drug delivery system is reported for gliomas (CZQD@HA@DOX), which aggregates multiple features such as the susceptible imaging tracer property due to the use of CZQD and the targeting of HA to the receptor cluster 44 (CD44) of glioma cells, which provides the system with the functions of targeted enrichment and precise drug delivery at the tumor site. The pH-responsive drug delivery system has not only an excellent encapsulation rate but also a high drug loading capacity, and the doxorubicin loaded on it can be released centrally at the tumor microenvironment site and causes an increase of reactive oxygen species in the mitochondria and trigger oxidative stress, which leads to high expression of Bax apoptotic proteins, ultimately activating the mitochondrial pathway-mediated apoptotic process in glioma cells. Overall, this drug delivery system has great potential for application in precision targeted therapy and visual tracer imaging of gliomas.

摘要

在恶性肿瘤之一的胶质瘤治疗中,尽管化疗是最常用的治疗方法,但它常常存在生物利用度低的问题。因此,提高药物的精准度和效率对胶质瘤治疗至关重要且极具挑战性。在此,报道了一种用于胶质瘤的先进药物递送系统(CZQD@HA@DOX),它具有多种特性,如由于使用了CZQD而具有灵敏的成像示踪特性,以及HA对胶质瘤细胞受体簇44(CD44)的靶向作用,这为该系统提供了在肿瘤部位靶向富集和精准药物递送的功能。这种pH响应性药物递送系统不仅具有出色的包封率,还具有高载药量,负载在其上的阿霉素可在肿瘤微环境部位集中释放,并导致线粒体中活性氧增加,引发氧化应激,从而导致促凋亡蛋白Bax高表达,最终激活胶质瘤细胞中线粒体途径介导的凋亡过程。总体而言,这种药物递送系统在胶质瘤的精准靶向治疗和可视化示踪成像方面具有巨大的应用潜力。

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