Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury

Mahasweta Das; Chunyan Wang; Raminder Bedi; Shyam S Mohapatra; Subhra Mohapatra

doi:10.1016/j.nano.2014.01.003

Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury

Nanomedicine. 2014 Oct;10(7):1539-48. doi: 10.1016/j.nano.2014.01.003. Epub 2014 Jan 29.

Authors

Mahasweta Das¹, Chunyan Wang², Raminder Bedi³, Shyam S Mohapatra⁴, Subhra Mohapatra⁵

Affiliations

¹ USF Morsani College of Medicine, Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, FL, USA; Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
² USF Morsani College of Medicine, Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, FL, USA; Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
³ Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
⁴ USF Morsani College of Medicine, Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, FL, USA; Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA. Electronic address: smohapat@health.usf.edu.
⁵ USF Morsani College of Medicine, Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, FL, USA; Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL, USA. Electronic address: smohapa2@health.usf.edu.

Abstract

Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body.

Keywords: Bio-distribution; Brain; DNA delivery; LFPI; Magnetic micelle; TBI; Theranostic.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Brain Injuries / therapy*
Cell Line
Contrast Media
DNA / administration & dosage*
Magnetic Resonance Imaging
Magnetics*
Male
Micelles*
Rats
Rats, Sprague-Dawley

Substances

Contrast Media
Micelles
DNA

Grants and funding

R01 CA152005/CA/NCI NIH HHS/United States