PUBLICATION
Enhanced blood-brain barrier penetration and glioma therapy mediated by T7 peptide-modified low-density lipoprotein particles
- Authors
- Liang, M., Gao, C., Wang, Y., Gong, W., Fu, S., Cui, L., Zhou, Z., Chu, X., Zhang, Y., Liu, Q., Zhao, X., Zhao, B., Yang, M., Li, Z., Yang, C., Xie, X., Yang, Y., Gao, C.
- ID
- ZDB-PUB-190316-14
- Date
- 2018
- Source
- Drug delivery 25: 1652-1663 (Journal)
- Registered Authors
- Zhao, Baoquan
- Keywords
- Low-density lipoprotein particles, T7 peptide, brain-targeted drug delivery, glioma, vincristine
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry*
- Angiogenesis Inhibitors/therapeutic use*
- Animals
- Antineoplastic Agents, Phytogenic/administration & dosage
- Antineoplastic Agents, Phytogenic/pharmacology
- Blood-Brain Barrier/metabolism*
- Brain Neoplasms/drug therapy*
- Brain Neoplasms/pathology
- Collagen Type IV/chemistry*
- Collagen Type IV/therapeutic use*
- Drug Carriers
- Drug Delivery Systems
- Excipients
- Female
- Glioma/drug therapy*
- Glioma/pathology
- Humans
- Lipoproteins, LDL/chemistry
- Mice
- Mice, Inbred ICR
- Nanoparticles
- Peptide Fragments/chemistry*
- Peptide Fragments/therapeutic use*
- Receptors, Transferrin/chemistry
- Vincristine/administration & dosage
- Vincristine/pharmacology
- Zebrafish
- PubMed
- 30394123 Full text @ Drug Deliv
Citation
Liang, M., Gao, C., Wang, Y., Gong, W., Fu, S., Cui, L., Zhou, Z., Chu, X., Zhang, Y., Liu, Q., Zhao, X., Zhao, B., Yang, M., Li, Z., Yang, C., Xie, X., Yang, Y., Gao, C. (2018) Enhanced blood-brain barrier penetration and glioma therapy mediated by T7 peptide-modified low-density lipoprotein particles. Drug delivery. 25:1652-1663.
Abstract
Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature and low permeability of drugs across the blood-brain barrier (BBB). An ideal glioma-targeted delivery system need to traverse the BBB and then target glioma cells with adequate optimized physiochemical properties and biocompatibility. However, it is an enormous challenge to the researchers to engineer the above-mentioned features into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. In this study, we demonstrate a strategy for glioma targeting by encapsulating vincristine sulfate (VCR) into a naturally available low-density lipoprotein particles (LDL)-based drug delivery system with the modification of T7 peptide ligand (T7-LDL). LDL, endogenous lipid transporters, can specifically bind to brain endothelial cells and glioma cells via interacting with the low-density lipoprotein receptors (LDLR). T7 is a seven-peptide ligand of transferrin receptors (TfR) capable of circumventing the BBB and then targeting glioma. By combining the dual-targeting delivery effect of T7 peptide and parent LDL, T7-LDL displayed higher glioma localization than that of parent LDL. After loading with VCR, T7-LDL showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that T7-LDL is an important potential drug delivery system for glioma-targeted therapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping