Dual-modified natural high density lipoprotein particles for systemic glioma-targeting drug delivery

Drug Delivery

Xiaoyang Chu¹  Xiangyang Xie²  Chunrong Yang³  Lian Yu³  Shiyao Fu⁴  Lin Cui⁴  Meiyan Yang⁵  Qianqian Liu⁵  Chunsheng Gao⁵  Wei Gong⁵  Yang Yang⁵  Zhiping Li⁵  Meng Liang⁵  Yuli Wang⁵  Zhide Su⁶ 

[1] 307 Hospital of the PLA, Beijing, China;Department of Pharmacy, Wuhan General Hospital of the PLA, Wuhan, Chin;Jiamusi University, Jiamusi, China;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;Weifang People’s Hospital, Weifang, China;

关键词: Natural high-density lipoprotein particles;    blood-brain barrier;    blood-brain tumor barrier;    glioma;    10-hydroxycamptothecin;   

DOI  :  10.1080/10717544.2018.1519002

来源: publisher

【 摘 要 】

Therapeutic outcome for the treatment of glioma was often limited due to the two barriers involved: the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). Therefore, the development of nanocarriers that possess both BBB and BBTB permeability and glioma-targeting ability is of great importance for the chemotherapy of glioma. New frontiers in nanomedicine are advancing the research of new biomaterials. Here we constructed a natural high-density lipoprotein particle (HDL)-based drug delivery system with the dual-modification of T7 and dA7R peptide ligand (T7/dA7R-HDL) to achieve the above goals. HDL, the smallest lipoprotein, plays a biological role and is highly suitable as a platform for delivering imaging and therapeutic agents. T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. dA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR 2) overexpressed on angiogenesis, presenting excellent glioma-homing property. 10-Hydroxycamptothecin (HCPT), a hydrophobic anti-cancer drug, was used as the model drug in this study. By combining the dual-targeting delivery effect, the dual-modified HDL displayed higher glioma localization than that of single ligand-modified HDL or free HCPT. After loading with HCPT, T7/dA7R-HDL showed the most favorable anti-glioma effect in vivo. These results demonstrated that the dual-targeting natural nanocarriers strategy provides a potential method for improving brain drug delivery and anti-glioma treatment efficacy.

【 授权许可】

CC BY