Brain-targeting mechanisms of lactoferrin-modified DNA-loaded nanoparticles

Rongqin Huang, Weilun Ke, Liang Han, Yang Liu, Kun Shao, Liya Ye, Jinning Lou, Chen Jiang, Yuanying Pei

Research output: Contribution to journalArticlepeer-review

Abstract

Ligand-mediated brain-targeting drug delivery is one of the focuses at present. Elucidation of exact targeting mechanisms serves to efficiently design these drug delivery systems. In our previous studies, lactoferrin (Lf) was successfully exploited as a brain-targeting ligand to modify cationic dendrimer-based nanoparticles (NPs). The mechanisms of Lf-modified NPs to the brain were systematically investigated in this study for the first time. The uptake of Lf-modified vectors and NPs by brain capillary endothelial cells (BCECs) was related to clathrin-dependent endocytosis, caveolae-mediated endocytosis, and macropinocytosis. The intracellular trafficking results showed that Lf-modified NPs could rapidly enter the acidic endolysosomal compartments within 5 mins and then partly escape within 30 mins. Both Lf-modified vectors and NPs showed higher blood-brain barrier-crossing efficiency than unmodified counterparts. All the results suggest that both receptor- and adsorptive-mediated mechanisms contribute to the cellular uptake of Lf-modified vectors and NPs. Enhanced brain-targeting delivery could be achieved through the synergistic effect of the macromolecular polymers and the ligand.

Original languageEnglish (US)
Pages (from-to)1914-1923
Number of pages10
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number12
DOIs
StatePublished - Dec 2009
Externally publishedYes

Keywords

  • Adsorptive-mediated mechanism
  • Brain-targeting gene delivery
  • Lf-modified nanoparticles
  • Receptor-mediated mechanism

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Brain-targeting mechanisms of lactoferrin-modified DNA-loaded nanoparticles'. Together they form a unique fingerprint.

Cite this