title: Engineered magnetic hybrid nanoparticles with enhanced relaxivity for tumor imaging.
abstract: Clinically used contrast agents for magnetic resonance imaging (MRI) suffer by the lack of specificity; short circulation time; and insufficient relaxivity. Here, a one-step combinatorial approach is described for the synthesis of magnetic lipid-polymer (hybrid) nanoparticles (MHNPs) encapsulating 5 nm ultra-small super-paramagnetic iron oxide particles (USPIOs) and decorated with Gd(3+) ions. The MHNPs comprise a hydrophobic poly(lactic acid-co-glycolic acid) (PLGA) core, containing up to ~5% USPIOs (w/w), stabilized by lipid and polyethylene glycol (PEG). Gd(3+) ions are directly chelated to the external lipid monolayer. Three different nanoparticle configurations are presented including Gd(3+) chelates only (Gd-MHNPs); USPIOs only (Fe-MHNPs); and the combination thereof (MHNPs). All three MHNPs exhibit a hydrodynamic diameter of about 150 nm. The Gd-MHNPs present a longitudinal relaxivity (r1 = 12.95 ± 0.53 (mM s)(-1)) about four times larger than conventional Gd-based contrast agents (r1 = 3.4 (mM s)(-1)); MHNPs have a transversal relaxivity of r2 = 164.07 ± 7.0 (mM s)(-1), which is three to four times larger than most conventional systems (r2 ~ 50 (mM s)(-1)). In melanoma bearing mice, elemental analysis for Gd shows about 3% of the injected MHNPs accumulating in the tumor and 2% still circulating in the blood, at 24 h post-injection. In a clinical 3T MRI scanner, MHNPs provide significant contrast confirming the observed tumor deposition. This approach can also accommodate the co-loading of hydrophobic therapeutic compounds in the MHNP core, paving the way for theranostic systems.
authors.affiliation: Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: Santosh
authors.initials: S
authors.lastname: Aryal
authors.forename: Jaehong
authors.initials: J
authors.lastname: Key
authors.forename: Cinzia
authors.initials: C
authors.lastname: Stigliano
authors.forename: Jeyarama S
authors.initials: JS
authors.lastname: Ananta
authors.forename: Meng
authors.initials: M
authors.lastname: Zhong
authors.forename: Paolo
authors.initials: P
authors.lastname: Decuzzi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D008545:Melanoma / Q000175:diagnosis; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D003287:Contrast Media; D011092:Polyethylene Glycols; D005682:Gadolinium
keywords: Contrast agents; Gd-DOTA; MRI; Polymeric particles; SPIO