Enhanced blood–brain barrier penetration and glioma therapy mediated by T7 peptide-modified low-density lipoprotein particles

Drug Delivery

Xiaoyang Chu¹  Xiong Zhao²  Xiangyang Xie²  Chunrong Yang³  Meiyan Yang⁴  Chunhong Gao⁴  Qianqian Liu⁴  Chunsheng Gao⁴  Wei Gong⁴  Yue Zhang⁴  Baoquan Zhao⁴  Yang Yang⁴  Zhenhan Zhou⁴  Zhiping Li⁴  Meng Liang⁴  Yuli Wang⁴  Lin Cui⁵  Shiyao Fu⁶ 

[1] 307 Hospital of the PLA, Beijing, China;Beijing Institute of Health Service and Transfusion Medicine, Beijing, Chin;Department of Pharmacy, Jiamusi University, Jiamusi, China;State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China;State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China;Department of Pharmacy, Jiamusi University, Jiamusi, China;State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China;Department of Pharmacy, Wuhan General Hospital of the PLA, Wuhan, China;

关键词: Low-density lipoprotein particles;    T7 peptide;    brain-targeted drug delivery;    glioma;    vincristine;   

DOI  :  10.1080/10717544.2018.1494223

来源: publisher

【 摘 要 】

Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature and low permeability of drugs across the blood-brain barrier (BBB). An ideal glioma-targeted delivery system need to traverse the BBB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. In this study, we demonstrate a strategy for glioma targeting by encapsulating vincristine sulfate (VCR) into a naturally available low-density lipoprotein particles (LDL)-based drug delivery system with the modification of T7 peptide ligand (T7-LDL). LDL, endogenous lipid transporters, can specifically bind to brain endothelial cells and glioma cells via interacting with the low-density lipoprotein receptors (LDLR). T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. By combining the dual-targeting delivery effect of T7 peptide and parent LDL, T7-LDL displayed higher glioma localization than that of parent LDL. After loading with VCR, T7-LDL showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that T7-LDL is an important potential drug delivery system for glioma-targeted therapy.

【 授权许可】

CC BY