Key Laboratory of Drug Targeting of Education Ministry, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, PR China.
Department of Pharmacy, West China Second University Hospital, Sichuan University, PR China; Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, PR China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, PR China.
Bioorg Med Chem. 2022 Sep 1;69:116893. doi: 10.1016/j.bmc.2022.116893. Epub 2022 Jun 20.
Chemotherapy is a conventional treatment for glioma, but its efficacy is greatly limited due to low blood-brain barrier (BBB) permeability and lack of specificity. Herein, intelligent and tumor microenvironment (TME)-responsive folic acid (FA) derivatives and mitochondria-targeting berberine (BBR) derivatives co-modified liposome coated with Tween 80 loading paclitaxel (PTX-Tween 80-BBR + FA-Lip) was constructed. Specifically speaking, liposomes modified by FA can be effectively target ed to glioma cells. BBR, due to its delocalized positive electricity and lipophilicity, can be attracted by mitochondrial membrane potential and concentrate on mitochondria to achieve mitochondrial targeting and induce cell apoptosis. By simultaneously modifying the liposome with FA and BBR to deliver drugs, leads to a good therapeutic effect of glioma through FA-based glioma targeting and BBR-based mitochondrial targeting. In addition, the surface of the liposome was coated with Tween 80 to further improve BBB penetration. All results exhibited that PTX-Tween 80-BBR + FA-Lip can observably improve the chemotherapy therapeutic efficacy through the highly specific tumor targeting and mitochondrial targeting, which can provide new ideas and methods for the targeted therapy of glioma.
化疗是治疗神经胶质瘤的常规方法，但由于血脑屏障（BBB）通透性低和缺乏特异性，其疗效受到极大限制。在此，构建了智能和肿瘤微环境（TME）响应的叶酸（FA）衍生物和线粒体靶向小檗碱（BBR）衍生物共修饰的 Tween 80 包载紫杉醇（PTX-Tween 80-BBR+FA-Lip）脂质体。具体来说，通过 FA 修饰的脂质体可以有效地靶向神经胶质瘤细胞。BBR 由于其离域正电荷和亲脂性，可以被线粒体膜电位吸引并聚集在线粒体上，从而实现线粒体靶向并诱导细胞凋亡。通过同时用 FA 和 BBR 修饰脂质体来递药，通过基于 FA 的神经胶质瘤靶向和基于 BBR 的线粒体靶向，实现了对神经胶质瘤的良好治疗效果。此外，脂质体表面用 Tween 80 包被以进一步提高 BBB 穿透性。所有结果均表明，PTX-Tween 80-BBR+FA-Lip 通过高度特异性的肿瘤靶向和线粒体靶向，显著提高了化疗疗效，为神经胶质瘤的靶向治疗提供了新的思路和方法。
