NANOSMARTS · Smart nondimensional biosensors for detection of tumor cells and cytotoxic amyloids intermediates

This project integrates the development of (a) bioconjugated silicon nanoparticles (NPs) as new, < 3nm, fluorescent probes and (b) dual-emission band fluorescent biosensors for protein conformation investigations to be applied in diagnostic procedures related to tumor biology and neurodegenerative diseases. Epidermal growth factor receptor (EGFR) is an important therapeutic target in a variety of tumors, particularly malignant gliomas where mutation and/or amplification of EGFR is often observed. The laboratory has demonstrated in a pilot study the specific binding of biomolecules conjugated to Quantum Dots to patient-derived glioma spheroids. High wavelength emitting QDs are necessary to distinguish binding from tissue autofluorescence but such QDs are large (~40 nm) and do not penetrate deeply into tissues or access cellular junctions. The project will develop smaller, more inert, and less toxic conjugated silicon nanoparticles that can ultimately be used for the detection of residual glioma cells in patients after surgical resection. Additionally, more complex composite nanoparticles that selectively internalize in the tumor cells will be investigated as vehicles for drug delivery or selective killing. The aggregation of proteins and peptides is a fundamental feature of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and spongiform encephalopathies. It is not clear whether the fibrillar aggregates or smaller forms of the implicated proteins are the cause of cytotoxicity. Both in vitro assays and in vivo studies are hampered by the lack of probes that can distinguish and quantitate early stages of the aggregation phenomenon. This project will develop fluorescent biosensors for protein folding on the basis of environment sensitive ratiometric dyes that exhibit dual emission. Such dyes are prospective tools for a development of facile and rapid assays for protein folding for application in diagnostics and drug screening assays.