Drug Delivery | |
Dual-modified natural high density lipoprotein particles for systemic glioma-targeting 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
【 预 览 】
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RO202004234291583ZK.pdf | 3192KB | download |