Abstract
A novel polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single polyacrylamide matrix (PolyAcrylamide Magnetic [PAM] nanoparticles). This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec(-1) mM(-1). Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa) to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.
Highlights
Advances in nanoparticle technology over the last decade have shown that some of these materials have the potential to play an important role in the diagnosis and treatment of cancers
The R1 values were in the range of 1.7 to 2.4 secÀ1 mMÀ1, which is significantly lower than R1 values measured in other superparamagnetic iron oxide (SPIO) preparations [21]
In Vivo Characterization of Nanoparticle Preparations The usefulness of SPIO nanoparticles depends on the ability of the nanoparticles to produce significant contrast enhancement in the tissue or tumor of interest
Summary
Advances in nanoparticle technology over the last decade have shown that some of these materials have the potential to play an important role in the diagnosis and treatment of cancers. Two generic types of magnetic nanoparticles have been used over the last two decades: primary iron oxide nanoparticles (the core of the nanoparticle consists of an iron oxide crystal, coated by a polymer) and polymeric nanoparticles that contain iron oxide crystals doped into their matrix. The former group of agents consists largely of dextran-coated iron oxide preparations, which are typically either monocrystalline (MION, CLIO) [13 – 19] or polycrystalline (PION) [13,19]. The iron oxide core is caged by the cross-linked dextran coating so that there exists no equilibrium between free and iron oxide-associated dextran moieties
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