Abstract 5299: A new class of multifunctional magnetic nanoconstructs for imaging and thermal ablation in cancer

Abstract

Abstract New paramagnetic nanoconstructs (nCS) are demonstrated with superior MRI and thermal ablation properties. The nCSs are generated by loading Gd-DTPA and ultra-short gadonanotubes (GNTs) within the nanoporous matrix of systemically injectable silicon nanoporous particles (SiNPs) [1]. Gd-DTPA is a Gd-based contrast agent currently used in clinical practice. The GNTs consist of Gd3+-ion clusters encapsulated within carbon nanotube capsules, which are 20-80 nm in length and 1.3 nm in diameter. Nanoporous discoidal SiNPs are fabricated by combining optical lithography and electrochemical etching. Two different particle sizes (small 600×200 nm and large 1000×400 nm) and particle surface configurations (untargeted and RGD-4C targeted) are considered in this study. The nCSs are characterized in terms of (i) biodistribution in tumor bearing mice; (ii) MRI longitudinal relaxivity r1 and (iii) thermal ablation efficiency. The nCS accumulation in 6 organs (liver, spleen, heart, lungs, kidneys and brain) and in tumors is quantified by elemental silicon analysis through inductively coupled plasma-optical emission spectrometer. Organ accumulation is observed to highly dependent on particle shape and size. In tumors, the larger discoidal particles are observed to accumulate more than the smaller particles, with a percentage of injected dose per gram organ of about 5% and 1.5%, respectively. For RGD-4C targeted particles, the tumor accumulation percentages grow up to about 10% and 8% of the injected dose / gram tumor, respectively. For MRI applications, the nCSs exhibit a relaxivity enhancement up to 3-4 times the values of the original Gd-based imaging agent loaded (either Gd-DTPA or GNT). In particular, for the GNT loaded SiNPs, longitudinal relaxivities up to 160 mM-1s-1 per Gd3+-ions are measured at 1.5T, which are two orders of magnitude higher than for clinically available MRI agents (r1 = 4 mM-1s-1 per Gd3+-ions at 1.5T). Eventually, the nCS thermal ablating properties are characterized upon excitation through externally applied electromagnetic fields. High quality-factor resonators (0.5-300 MHz) with separated radio frequency -electric (up to 200 V/m) and -magnetic (up to 5 mT) fields are used for non-invasive nCS stimulation and fiber optic temperature sensors are used to map the associated temperature increase. The nCSs have shown both magnetic and dielectric rf losses and significant heating at 120 MHz. Mechanisms and efficiency of heating are discussed in terms of both magnetic and electric fields excitation, the concentration of nCSs, loading of GNTs into nCSs, frequency and power of the external generator.The multifunctionality and superior biodistribution performance of these nCSs could be effectively used in cancer imaging and treatment through alternative physical-based approaches. [1] Ananta JS,…, Decuzzi P. Nat Nanotechnol. 2010;5:815-21 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5299. doi:10.1158/1538-7445.AM2011-5299