Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.
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.
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.
Mahasweta
M
Das
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.
Chunyan
C
Wang
Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
Raminder
R
Bedi
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.
Shyam S
SS
Mohapatra
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.
Subhra
S
Mohapatra
D000818:Animals; D001930:Brain Injuries / Q000628:therapy*; D002460:Cell Line; D003287:Contrast Media; D004247:DNA / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D008823:Micelles; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D008823:Micelles; D004247:DNA
Bio-distribution; Brain; DNA delivery; LFPI; Magnetic micelle; TBI; Theranostic