Glioma targeting peptide modified apoferritin nanocage.

Abstract

Therapeutic outcome for the treatment of glioma was often limited due to the non-targeted nature of drugs and the physiological barriers, including the blood-brain barrier (BBB) and the blood-brain tumor barrier (BBTB). An ideal glioma-targeted delivery system must be sufficiently potent to cross the BBB and BBTB 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 apoferritin nanocage-based drug delivery system with the modification of GKRK peptide ligand (GKRK-APO). Apoferritin (APO), an endogenous nanosize spherical protein, can specifically bind to brain endothelial cells and glioma cells via interacting with the transferrin receptor 1 (TfR1). GKRK is a peptide ligand of heparan sulfate proteoglycan (HSPG) over-expressed on angiogenesis and glioma, presenting excellent glioma-homing property. By combining the dual-targeting delivery effect of GKRK peptide and parent APO, GKRK-APO displayed higher glioma localization than that of parent APO. After loading with VCR, GKRK-APO showed the most favorable antiglioma effect in vitro and in vivo. These results demonstrated that GKRK-APO is an important potential drug delivery system for glioma-targeted therapy.

• Authors: Meifang Zhai, Yuli Wang, Ligang Zhang, Meng Liang, Shiyao Fu, Lin Cui, Meiyan Yang, Wei Gong, Zhiping Li, Lian Yu, Xiangyang Xie, Chunrong Yang, Yang Yang, Chunsheng Gao
• Journal: Drug delivery (Drug Deliv) Vol. 25 Issue 1 Pg. 1013-1024 (Nov 2018) ISSN: 1521-0464 [Electronic] England
• PMID: 29726297 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Antineoplastic Agents
• Drug Carriers
• Peptides
• Vincristine
• Apoferritins

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoferritins (pharmacology)
• Blood-Brain Barrier (metabolism)
• Brain (drug effects, metabolism)
• Brain Neoplasms (drug therapy, metabolism)
• Cell Line
• Cell Line, Tumor
• Drug Carriers (chemistry)
• Drug Delivery Systems (methods)
• Endothelial Cells
• Female
• Glioma (drug therapy, metabolism)
• Human Umbilical Vein Endothelial Cells
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (administration & dosage)
• Peptides (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Vincristine (pharmacology)