Abstract

There have been a significant number of recent advances in the design and testing of nanoscale targeting systems. True nanoscale systems having payloads that are 100nm or less include protein nucleic acid assemblies, dendrimers, viral capsids, milled boron carbide and gold nanoparticles. Many of these systems show promise in the diagnosis and treatment of a variety of medical conditions. For diagnostic and prognostic purposes the payload can consist of a simple easily detectable chromospheres. Many of biomarkers of both the tumor and its microenvironment are expected to involve differential expression of divalent proteins capable of protein or peptide ligand interaction. In my laboratory we are developing multivalent nanodevices designed to bind multimeric targets for use in identifying new biomarkers in prostate cancer. Our approach is based in a system for addressing fusion proteins to DNA scaffolds and the tools for characterizing the resulting nucleoprotein assemblies. In recent work we compared chemically fluoresceinated ligand (thioredoxin) with a multivalent nanodevice displaying three thioredoxin ligands in binding to human cancer cells and frozen tissue sections. Our findings demonstrate that not only does the multivalent nanodevice more effectively label prostate cancer associated stromal cells than the cognate monovalent ligand, but also that it identifies dimeric thioredoxin reductases 1 and 2 as potential biomarkers of reactive stroma in the prostate tumor microenvironment. Our data suggest that the nanodevice has potential utility as prognostic marker of prostate cancer and a vehicle to therapeutically target the prostate cancer microenvironment. Nanotechnology for Cancer Biomarker Discovery Steven S. Smith Beckman Research Institute of the City of Hope, USA doi:10.4172/2155-9929.1000003

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