Investigation Of The Permeation And Retention Of Biocompatible Low-Retention Superparamagnetic Iron Oxide Nanoclusters In Tumors With Magnetic Resonance Imaging

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PASuperparamagnetic iron oxide (SPIO) nanoclusters assembled with poly-L-lysine (PLL) and hydroxyl starch show a unique bioclearance property with low retention in the liver and spleen and effective renal excretion. In the orthotopic liver tumor model, the assembled low retention biocompatible SPIO nanoclusters exhibit a high contrast enhancing capability in T2-weighted magnetic resonance imaging (MRI) at a low dose. For the orthotopic liver tumor, the T2-weighted MRI with SPIO nanoclusters is a negative imaging method to reduce the signal intensity of the normal liver tissue, whereas the potential of the retention and permeability of SPIO nanoclusters in tumors was not fully assessed. The latter becomes critically important for diagnosis and prognosis of pancreatic and prostate tumors in the non-reticuloendothelial system. Two approaches of tumor targeting were investigated and compared in this study including the passive targeting via the EPR effect of nanoparticles and the active targeting by the tumor-specific ligands such as TAT, iRGD and pH sensitive peptides. The accumulation of SPIO nanoclusters in tumors was assessed in the subcutaneous pancreatic and prostate tumor models with MRI over times, iron levels and pathological assessment. Our results showed that the retention and permeation of SPIO nanoclusters varied with multiple factors of tumors. For example, well developed tumors with large necrosis core tended to have a high level of SPIO accumulation. In contrast, the early stage solid tumor had minimal retention of SPIOs. Similar effects have been observed in both passive and active tumor targeting by SPIO nanoclusters. Moreover, the accumulation of SPIOs in tumor was achieved over a longer time period over 24 to 48 h with long retention as compared with those in the normal liver, lung, and spleen tissue (between 30 min to 3 h) with rapid clearance. Our data suggested that with well-designed tumor targeting, the biocompatible low-retention SPIO nanoclusters could be an effective MRI contrast agent for MRI of pancreatic and prostate tumors.Citation Format: Yushuang Wei, Liang Shan, Paul Wang, Qibing Zhou. Investigation of the permeation and retention of biocompatible low-retention superparamagnetic iron oxide nanoclusters in tumors with magnetic resonance imaging. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1479. doi:10.1158/1538-7445.AM2015-1479