Abstract 4295: Multifunctional nanoconstructs for tumor visualization using contrast enhanced MRI

Abstract

Abstract New multifunctional nanoconstructs using mesoporous Si particles (SiMPs) and polymeric hydrogel particles (HG) are synthesized with superior MRI efficacy and favorable pharmacokinetic properties. Clinically relevant Gd3+-based contrast agents (CAs) for magnetic resonance imaging (MRI), namely [Gd (DTPA)]2−, [Gd (DOTA)]1- and superparamagnetic iron oxide (SPIO) nanoparticles, were either i) encapsulated within the mesoporous structure of the SiMPs or ii) covalently attached to SiMPs and HGs. The size (from 400 to 2000 nm) and shape (discoidal, cylindrical, etc.) of the nanoconstructs are accurately tailored during the fabrication process to control the in vivo biodistribution. In tumor bearing mouse model, discoidal particles with a characteristic size of 1000 x 400 nm were found to accumulate at the tumor site more than other particles. The incorporation of clinically used, FDA approved CAs into the mesoporous structure of the SiMPs led to magnetic nanoconstructs exhibiting much higher relaxivities as compared to free CAs in solution. In particular, the relaxivity for [Gd (DTPA)]2− and [Gd (DOTA)]−1 loaded SiMPs was measured to be ∼ 25 mM−1s−1, which is more than 6 times larger than the r1 obtained for free CAs (∼ 4 mM−1s−1). The pore size played a dominant role in that the relaxivity was observed to grow with a reduction in pore diameter: r1 ∼ 24 mM−1s−1 for small pore SiMPs (5-10 nm); and r1 ∼ 10 mM−1s−1 for huge pore SiMPs (30-40 nm). CAs covalently attached to SiMPs and HGs, exhibited no such dependence on pore sizes but provided comparable enhancement in r1. For SPIOs encapsulated in mesoporous SiMPs, a much larger enhancement in relaxivity was observed with r2 ∼ 220 mM−1s−1 for the resulting nanoconstructs against r2 ∼ 11.2 mM−1s−1 for free SPIOs. These results suggest that geometrical confinement into mesopores is a general strategy for enhancing the performance of both T1 and T2 MRI CAs. Intravenous injection of SPIO-loaded SiMPs in melanoma bearing mice decreased the contrast (T2-weigthed relaxation), confirming the high level of accumulation of these nanoconstructs at the tumor site. For the enhanced relaxivity and superior localization of imaging agents at the target site, the proposed nanoconstructs provide an ideal platform for early cancer detection by MRI. In addition, the easily functionalizable surface of these nanoconstructs render them the ability to perform cellular and molecular imaging using clinical MRI scanners. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4295. doi:1538-7445.AM2012-4295