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 5nm ultra-small super-paramagnetic iron oxide particles (USPIOs) and decorated with Gd3+ 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). Gd3+ ions are directly chelated to the external lipid monolayer. Three different nanoparticle configurations are presented including Gd3+ chelates only (Gd-MHNPs); USPIOs only (Fe-MHNPs); and the combination thereof (MHNPs). All three MHNPs exhibit a hydrodynamic diameter of about 150nm. The Gd-MHNPs present a longitudinal relaxivity (r1=12.95±0.53 (mms)-1) about four times larger than conventional Gd-based contrast agents (r1=3.4 (mms)-1); MHNPs have a transversal relaxivity of r2=164.07±7.0 (mms)-1, which is three to four times larger than most conventional systems (r2~50 (mms)-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 24h 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.
|Number of pages||8|
|Publication status||Published - 2013 Oct|
Bibliographical noteFunding Information:
This work is partially supported by the Cancer Prevention Research Institute of Texas through the grant CPRIT RP110262 and The Methodist Hospital Research Institute .
All Science Journal Classification (ASJC) codes
- Ceramics and Composites
- Mechanics of Materials