PUBLICATION

Apoferritin Nanocage for Brain Targeted Doxorubicin Delivery

Authors
Chen, Z., Zhai, M., Xie, X., Zhang, Y., Ma, S., Li, Z., Yu, F., Zhao, B., Zhang, M., Yang, Y., Mei, X.
ID
ZDB-PUB-180515-14
Date
2017
Source
Molecular pharmaceutics   14: 3087-3097 (Journal)
Registered Authors
Zhang, Min, Zhao, Baoquan
Keywords
apoferritin nanocage, blood−brain barrier, brain-targeted delivery, glioma
MeSH Terms
  • Animals
  • Antigens, CD/metabolism
  • Apoferritins/chemistry*
  • Blood-Brain Barrier/metabolism
  • Brain/metabolism*
  • Brain Neoplasms/drug therapy
  • Brain Neoplasms/metabolism
  • Cell Line
  • Doxorubicin/administration & dosage*
  • Doxorubicin/chemistry
  • Doxorubicin/therapeutic use
  • Drug Carriers/chemistry*
  • Drug Delivery Systems/methods
  • Glioma/drug therapy
  • Glioma/metabolism
  • Mice
  • Nanostructures/chemistry*
  • Receptors, Transferrin/metabolism
  • Zebrafish
PubMed
28728419 Full text @ Mol. Pharm.
Abstract
An ideal brain-targeted nanocarrier must be sufficiently potent to penetrate the blood-brain barrier (BBB) and sufficiently competent to target the cells of interest with adequate optimized physiochemical features and biocompatibility. However, it is an enormous challenge to the researchers to organize the above-mentioned properties into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. Herein, we demonstrate a straightforward strategy for brain targeting by encapsulating doxorubicin (DOX) into a naturally available and unmodified apoferritin nanocage (DOX-loaded APO). APO can specifically bind to cells expressing transferrin receptor 1 (TfR1). Because of the high expression of TfR1 in both brain endothelial and glioma cells, DOX-loaded APO can cross the BBB and deliver drugs to the glioma with TfR1. Subsequent research demonstrated that the DOX-loaded APO had good physicochemical properties (particle size of 12.03 ± 0.42 nm, drug encapsulation efficiency of 81.8 ± 1.1%) and significant penetrating and targeting effects in the coculture model of bEnd.3 and C6 cells in vitro. In vivo imaging revealed that DOX-loaded APO accumulated specifically in brain tumor tissues. Additionally, in vivo tumor therapy experiments (at a dosage of 1 mg/kg DOX) demonstrated that a longer survival period was observed in mice that had been treated with DOX-loaded APO (30 days) compared with mice receiving free DOX solution (19 days).
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping