Suppr超能文献

中性粒细胞高效递送光敏剂用于胶质母细胞瘤的靶向光动力治疗

Efficient Photosensitizer Delivery by Neutrophils for Targeted Photodynamic Therapy of Glioblastoma.

作者信息

Wen Ruojian, Liu Yuwei, Tian Xiang, Xu Yonghong, Chen Xiao

机构信息

Department of Physiology, School of Medicine, Jianghan University, Wuhan 430056, China.

Department of Anatomy, School of Medicine, Jianghan University, Wuhan 430056, China.

出版信息

Pharmaceuticals (Basel). 2025 Feb 19;18(2):276. doi: 10.3390/ph18020276.

Abstract

Glioblastoma (GBM) is the deadliest type of brain tumor and photodynamic therapy (PDT) is a promising treatment modality of GBM. However, insufficient photosensitizer distribution in the GBM critically limits the success of PDT. To address this obstacle, we propose tumoritropic neutrophils (NE) as active carriers for photosensitizer delivery to achieve GBM-targeted PDT. Isolated mouse NE were loaded with functionalized hexagonal boron nitride nanoparticles carrying the photosensitizer chlorin e6 (BNPD-Ce6). In vitro experiments were conducted to determine drug release from the loaded NE (BNPD-Ce6@NE) to mouse GBM cells and consequential photo-cytotoxicity. In vivo experiments were performed on mice bearing intracranial graft GBMs to demonstrate GBM-targeted drug delivery and the efficacy of anti-GBM PDT mediated by BNPD-Ce6@NE. BNPD-Ce6@NE displayed good viability and migration ability, and rapidly released BNPD-Ce6 to co-cultured mouse GBM cells, which then exhibited marked reactive oxygen species (ROS) generation and cytotoxicity following 808 nm laser irradiation (LI). In the in vivo study, a single intravenous bolus injection of BNPD-Ce6@NE resulted in pronounced Ce6 distribution in intracranial graft GBMs 4 h post injection, which peaked around 8 h post injection. A PDT regimen consisting of multiple intravenous BNPD-Ce6@NE injections each followed by one extracranial tumor-directed LI 8 h post injection significantly slowed the growth of intracranial graft GBMs and markedly improved the survival of host animals. Histological analysis revealed massive tumor cell damage and NE infiltration in the PDT-treated GBMs. NE are efficient carriers for GBM-targeted photosensitizer delivery to achieve efficacious anti-GBM PDT.

摘要

胶质母细胞瘤(GBM)是最致命的脑肿瘤类型,光动力疗法(PDT)是一种有前景的GBM治疗方式。然而,GBM中光敏剂分布不足严重限制了PDT的成功。为解决这一障碍,我们提出将肿瘤趋向性中性粒细胞(NE)作为光敏剂递送的活性载体,以实现针对GBM的PDT。分离的小鼠NE负载了携带光敏剂二氢卟吩e6(BNPD-Ce6)的功能化六方氮化硼纳米颗粒。进行体外实验以确定负载的NE(BNPD-Ce6@NE)向小鼠GBM细胞的药物释放以及随之产生的光细胞毒性。对患有颅内移植GBM的小鼠进行体内实验,以证明针对GBM的药物递送以及由BNPD-Ce6@NE介导的抗GBM PDT的疗效。BNPD-Ce6@NE表现出良好的活力和迁移能力,并迅速将BNPD-Ce6释放到共培养的小鼠GBM细胞中,在808 nm激光照射(LI)后,这些细胞随后表现出明显的活性氧(ROS)生成和细胞毒性。在体内研究中,单次静脉推注BNPD-Ce6@NE导致注射后4小时颅内移植GBM中有明显的Ce6分布,在注射后约8小时达到峰值。由多次静脉注射BNPD-Ce6@NE组成的PDT方案,每次注射后8小时进行一次颅外肿瘤定向LI,显著减缓了颅内移植GBM的生长,并显著提高了宿主动物的存活率。组织学分析显示,在PDT治疗的GBM中存在大量肿瘤细胞损伤和NE浸润。NE是用于针对GBM的光敏剂递送以实现有效的抗GBM PDT的有效载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4aa1/11859058/292913a3e135/pharmaceuticals-18-00276-g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验