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Development of nanoencapsulated cancer-specific contrast agent for magnetic resonance imaging
EP39426
Poster Title: Development of nanoencapsulated cancer-specific contrast agent for magnetic resonance imaging
Submitted on 20 Oct 2022
Author(s): Joel Slaton, Bruce Hammer, Gregory Metzger, Gretchen Unger,
Affiliations: Univ. MN, VAMC, Minneapolis,MN;GeneSegues, Chaska MN
This poster was presented at AACR 2009
Poster Views: 289
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Poster Information
Abstract: Current magnetic resonance (MR) contrast agents utilize vascular spaces to visualize and enhance neoplasms. The s50 capsule (sub-50 nanometer capsule) is a novel delivery technology capable of intracellular delivery of large cargos in a tissue- and cell-specific manner. These nanocapsules derive their specificity from a coating of ligands (here, TBG or tenfibgen, the fibrinogen fragment of tenascin), that have the potential to specifically target tumors. We are developing nanoencapsulated MR agents that can be delivered intracellularly to enhance MR imaging of localized and metastatic cancer. We prepared TBG-coated ferrous oxide (FeO) nanoparticles and compared them by i) morphology (atomic force microscopy, ii) surface charge (zeta potential by dynamic light scattering) iii) incorporation ( ICP-AES), iv) cellular proliferation by thymidine incorporation and v) cellular uptake by iron histology. We found that although incorporation is lower than for nucleic acid cargos (1-5% vs 70-90%), s50 capsule targeting is effective to provide sufficient cellular accumulation for histology as well as functional imaging at greatly reduced dosing levels. Importantly, consistent with radiolabel biodistribution studies using TBG-coated s50 capsules bearing I-128 labeled siRNA showing accumulation in injection site, tumor and enlarged (metastatic) lymph nodes, we also observed a decrease in T2-weighted contrast in liver nodules from mice bearing large PC3-LN4 subcutaneous tumors. Both radiolabel studies with a nucleic acid cargo and functional MRI imaging studies with a T2-weighted contrast agent (FeO Dextran) support the observation of no non- specific accumulation of these s50 capsules in the organs of the reticuloendothelial system. In conclusion, we have adapted a scalable, target-specific core-shell nanocapsule chemistry originally applied to nucleic acid delivery, and developed a nanoencapsulated FeO agent that is taken up intracellularly in primary and disseminated tumors and surprisingly produces a detectable MR signal change. Future work will focus on continued development of s50 TBG Ferric Dextran as well as candidate agents that can produce a T1-weighted positive signal change on MRI.
Summary: The development of a novel tumor-targeted nano capsule MRI agent is describedReferences: See within posterReport abuse »
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