title: Dual-purpose magnetic micelles for MRI and gene delivery.
abstract: Gene therapy is a promising therapeutic approach for treating disease, but the efficient delivery of genes to desired locations with minimal side effects remains a challenge. In addition to gene therapy, it is also highly desirable to provide sensitive imaging information in patients for disease diagnosis, screening and post-therapy monitoring. Here, we report on the development of dual-purpose chitosan and polyethyleneimine (PEI) coated magnetic micelles (CP-mag-micelles) that can deliver nucleic acid-based therapeutic agents and also provide magnetic resonance imaging (MRI). These 'theranostic' CP-mag-micelles are composed of monodisperse hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) loaded into the cores of micelles that are self-assembled from a block copolymer of poly (D, L-lactide) (PLA) and monomethoxy polyethylene glycol (mPEG). For efficient loading and protection of the nucleic acids the micelles were coated with cationic polymers, such as chitosan and PEI. The morphology and size distribution of the CP-mag-micelles were characterized and their potential for use as an MRI-probe was tested using an MRI scanner. The T(2) relaxivity of mag-micelles was similar to CP-mag-micelles confirming that coating with cationic polymers did not alter magnetism. Nanoparticles coated with chitosan:PEI at a weight ratio of 5:5 showed higher transfection efficiency in HEK293, 3T3 and PC3 cells than with weight ratios of 3:7 or 7:3. CP-mag-micelles are biocompatible, can be delivered to various organs and are safe. A single injection of CP-mag-micelles carrying reporter plasmids in vivo expressed genes for at least one week. Collectively, our results demonstrate that a structural reinforcement of SPIONs loaded in the core of an mPEG-PLA micelle coated with cationic polymers provides efficient DNA delivery and enhanced MRI potential, and affords a promising candidate for theranostics in the future.
authors.affiliation: Molecular Medicine Department, College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.forename: Sowndharya
authors.initials: S
authors.lastname: Ravi
authors.forename: Gary V
authors.initials: GV
authors.lastname: Martinez
authors.forename: Vignesh
authors.initials: V
authors.lastname: Chinnasamy
authors.forename: Payal
authors.initials: P
authors.lastname: Raulji
authors.forename: Mark
authors.initials: M
authors.lastname: Howell
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Davis
authors.forename: Jaya
authors.initials: J
authors.lastname: Mallela
authors.forename: Mohindar S
authors.initials: MS
authors.lastname: Seehra
authors.forename: Subhra
authors.initials: S
authors.lastname: Mohapatra
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods*
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D008823:Micelles; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA; D048271:Chitosan