Dual-modified liposome codelivery of doxorubicin and vincristine improve targeting and therapeutic efficacy of glioma |
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| Authors: | Yue Zhang Meifang Zhai Zhijiang Chen Xiaoyang Han Fanglin Yu |
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| Institution: | 1. State key Laboratory of Toxicology and Medical Countermeasure, Department of Pharmaceutics, Beijing Institute of Pharmacology and Toxicology, Beijing, PR China;2. Hubei University of Science and Technology, Xianning, PR China;3. Jiamusi University, Jiamusi, PR China;4. Outpatient Department of Beijing Space City, Aerospace Systems Divison, PLA Strategic Support Force, Beijing, PR China |
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| 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. |
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| Keywords: | T7 peptide DA7R peptide brain targeted drug delivery glioma doxorubicin vincristine |
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