Zhang Yue, Zhai Meifang, Chen Zhijiang, Han Xiaoyang, Yu Fanglin, Li Zhiping, Xie Xiangyang, Han Cuiyan, Yu Lian, Yang Yang, Mei Xingguo
a State key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics , Beijing Institute of Pharmacology and Toxicology , Beijing , PR China.
b Hubei University of Science and Technology , Xianning , PR China.
Drug Deliv. 2017 Nov;24(1):1045-1055. doi: 10.1080/10717544.2017.1344334.
Therapeutic outcome for the treatment of glioma was often limited due to drug resistance and low permeability of drug across the multiple physiological barriers, including the blood-brain barrier (BBB), and the blood-tumor barrier (BTB). In order to overcome these hurdles, we designed T7 and A7R dual peptides-modified liposomes (abbreviated as T7/A7R-LS) to efficiently co-delivery doxorubicin (DOX) and vincristine (VCR) to glioma in this study. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. A7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect, the dual-modified liposomes displayed higher glioma localization than that of single ligand-modified liposomes or free drug. After loading with DOX and VCR, T7/A7R-LS showed the most favorable antiglioma effect in vivo. In conclusion, this dual-targeting, co-delivery strategy provides a potential method for improving brain drug delivery and antiglioma treatment efficacy.
由于耐药性以及药物穿过包括血脑屏障(BBB)和血肿瘤屏障(BTB)在内的多种生理屏障的低渗透性,胶质瘤的治疗效果常常受到限制。为了克服这些障碍,在本研究中我们设计了T7和A7R双肽修饰的脂质体(简称为T7/A7R-LS),以有效地将阿霉素(DOX)和长春新碱(VCR)共同递送至胶质瘤。T7是转铁蛋白受体(TfR)的七肽配体,能够绕过血脑屏障并靶向胶质瘤。A7R是血管内皮生长因子受体2(VEGFR 2)的d肽配体,在血管生成中过表达,具有出色的胶质瘤归巢特性。通过结合双靶向递送效应,双修饰脂质体比单配体修饰脂质体或游离药物表现出更高的胶质瘤定位。在装载DOX和VCR后,T7/A7R-LS在体内显示出最有利的抗胶质瘤效果。总之,这种双靶向、共同递送策略为改善脑内药物递送和抗胶质瘤治疗效果提供了一种潜在方法。