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


ABSTRACT: 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.

SUBMITTER: Cui L 

PROVIDER: S-EPMC6263114 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Cui Lin L   Wang Yuli Y   Liang Meng M   Chu Xiaoyang X   Fu Shiyao S   Gao Chunsheng C   Liu Qianqian Q   Gong Wei W   Yang Meiyan M   Li Zhiping Z   Yu Lian L   Yang Chunrong C   Su Zhide Z   Xie Xiangyang X   Yang Yang Y   Gao Chunsheng C  

Drug delivery 20181101 1


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 de  ...[more]

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