Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma

Yue Zhang; Meifang Zhai; Zhijiang Chen; Xiaoyang Han; Fanglin Yu; Zhiping Li; Xiangyang Xie; Cuiyan Han; Lian Yu; Yang Yang; Xingguo Mei

doi:10.1080/10717544.2017.1344334

Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma

Drug Deliv. 2017 Nov;24(1):1045-1055. doi: 10.1080/10717544.2017.1344334.

Authors

Yue Zhang^{1

2}, Meifang Zhai^{1

3}, Zhijiang Chen^{1

2}, Xiaoyang Han⁴, Fanglin Yu¹, Zhiping Li¹, Xiangyang Xie⁵, Cuiyan Han⁶, Lian Yu³, Yang Yang¹, Xingguo Mei¹

Affiliations

¹ a State key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics , Beijing Institute of Pharmacology and Toxicology , Beijing , PR China.
² b Hubei University of Science and Technology , Xianning , PR China.
³ c Jiamusi University , Jiamusi , PR China.
⁴ d Outpatient Department of Beijing Space City , Aerospace Systems Divison, PLA Strategic Support Force , Beijing , PR China.
⁵ e Department of Pharmacy , Wuhan General Hospital of the Chinese People's Liberation Army , Wuhan , PR China.
⁶ f School of Pharmacy , Qiqihar Medical University , Qiqihar , PR China.

Abstract

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 ^DA7R dual peptides-modified liposomes (abbreviated as T7/^DA7R-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. ^DA7R 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/^DA7R-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.

Keywords: DA7R peptide; T7 peptide; brain targeted drug delivery; doxorubicin; glioma; vincristine.

MeSH terms

Brain Neoplasms
Cell Line, Tumor
Doxorubicin
Drug Delivery Systems
Glioma*
Humans
Liposomes
Vascular Endothelial Growth Factor A
Vincristine

Substances

Liposomes
Vascular Endothelial Growth Factor A
Vincristine
Doxorubicin

Grants and funding

We are grateful for the financial support from the Beijing Science and Technology New Star (Grant No. Z161100004916162), Beijing Natural Science Foundation (Grant No. 7172162), Natural Science Foundation of Hubei Province (Grant No. 2016CF198), the Health & Family Planning Commission of Hubei Province (Grant No. WJ2017Q031), Nature Science Foundation of Heilongjiang Province (Grant No. H2015070), and National Science and Technology Major Projects for ‘Major New Drugs Innovation and Development’ (Grant No. 2017ZX09101005-008-001).