Membrane Functionalized Nanoparticles for Ligand Screening

Radioisotope (RI) labels remain a critical tool for drug discovery applications, particularly for measuring analytes that are not detectable by traditional optical microscopy or electrochemical methods. Drug discovery applications require minimal perturbation of the compounds of interest, preventing the use of large labels that significantly change the structure and properties of the compounds, particularly for small molecules. RI labels play a fundamental role in the high-sensitivity detection of compounds as diverse as small molecule enzyme inhibitors, receptor agonists and antagonists, carbohydrates and carbohydrate derivatives, proteins, and many others. RIs facilitate highly sensitive detection with minimal perturbation of the size and structure of the analyte, compared to fluorescent labels, a particularly important property in drug discovery applications. RI labels provide unparalleled sensitivity and precision for ligand-receptor binding assays, including G-protein coupled receptor assays. Unfortunately, the low energy and short penetration depth of most common, biologically relevant RIs also complicate detection, limiting the capabilities for this approach. Scintillation Nanotechnologies, INC was founded in 2018 around a series of patent-pending, radioisotope- responsive, hybrid nanomaterials. that overcome several key limitations associated with traditional radioisotope counting methods. Scintillation Nanotechnologies has developed a novel nanomaterial, termed nanoSPA, for sensitive detection of low-energy radioisotopes in intracellular environments. nanoSPA presents a number of advantages compared to other methods for imaging small molecules, including a) enhanced compatibility with aqueous samples; b) a high-surface area to volume (SA/V) ratio to enhance β-particle detection; c) an easily modified surface for attachment of biomolecules and other chemical species; d) more reproducible surface chemistry. In this SBIR application, we propose to further develop nanoSPA with an emphasis on enhanced surface functionalization using a diverse range of critically needed surface functionalities and to characterize the resulting nanoSPA materials with respect to key quantitative criteria necessary to demonstrate the key commercial potential of this platform. Once successfully developed, nanoSPA will provide an important new tool for biomedical research.Project Narrative – Public Health Relevance: This research project will lead to further development of a new category of radioisotope-responsive sensors that can be used for chemically selective detection of radioisotope labeled compounds in advanced bio/chemical and biological assays. The capabilities afforded by this research will play a pivotal role in disease-relevant signal transduction research, drug discovery, clinical evaluation and many other key applications.