Zong Taili, Mei Ling, Gao Huile, Shi Kairong, Chen Jiantao, Wang Yang, Zhang Qianyu, Yang Yuting, He Qin
Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China; Chongqing Pharmaceutical Research Institute Company, Ltd., Chongqing 400061 China.
Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
J Pharm Sci. 2014 Dec;103(12):3891-3901. doi: 10.1002/jps.24186. Epub 2014 Oct 22.
The development of a drug delivery strategy that can not only cross the blood-brain barrier (BBB) rapidly, but also target the glioma and reach the core of glioma is essential and important for glioma treatment. To achieve this goal, we established a dual-targeting liposomal system modified with TAT (AYGRKKRRQRRR) and T7 (HAIYPRH), in which the specific ligand T7 could target BBB and brain glioma tumor and the nonspecific ligand TAT could enhance the effect of passing through BBB, and elevate the penetration into the tumor. The dual-targeting effects were evaluated by both in vitro and in vivo experiments. To identify the targeting effect, in vitro cellular uptake and BBB model were performed. Tumor spheroid penetration was performed to evaluate the penetration characteristics of the dual-targeting liposomes. In vivo pharmacokinetic studies were utilized to evaluate the influence of T7 and TAT peptides on the behavior of nanoparticle drug delivery system, and tissue distribution was further utilized to evaluate the glioma-targeting efficiency of the dual-targeting liposomes.
开发一种不仅能快速穿过血脑屏障（BBB），还能靶向胶质瘤并到达胶质瘤核心的药物递送策略，对于胶质瘤治疗至关重要。为实现这一目标，我们建立了一种用TAT（AYGRKKRRQRRR）和T7（HAIYPRH）修饰的双靶向脂质体系统，其中特异性配体T7可靶向血脑屏障和脑胶质瘤肿瘤，非特异性配体TAT可增强穿过血脑屏障的效果，并提高对肿瘤的渗透。通过体外和体内实验评估双靶向效果。为确定靶向效果，进行了体外细胞摄取和血脑屏障模型实验。进行肿瘤球体渗透实验以评估双靶向脂质体的渗透特性。利用体内药代动力学研究评估T7和TAT肽对纳米颗粒药物递送系统行为的影响，并进一步利用组织分布评估双靶向脂质体的胶质瘤靶向效率。
