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(80b) Novel Light-Activated Therapy for Mutli-Drug Resistant Pathogens

Nagpal, P., University of Colorado
Goodman, S., University of Colorado Boulder
Courtney, C., University of Colorado Boulder
Chatterjee, A., University of Colorado Boulder

Current design of therapeutics (drugs and nanoparticle-based therapies) relies heavily on a spatially selective drug-delivery system (colloids and vesicles coated with desired antibodies or proteins) due to non-specificity of the drugs or metal nanoparticles. Typically, these non-specific drugs once spatially delivered kill the targeted cells (e.g. tumor or pathogen) as well as healthy cells in close proximity (including metal nanopartciles used for cancer therapy). Further complexities in non-specific binding and incorrect delivery can cause undesirable side-effects. Here we present a novel nanoparticle-based therapy where the (non-metallic) nanoparticles specifically target selective cell phenotypes, based on their biochemical potentials. Using a specific light induced targeting mechanism, these light-activated reactive species (LARS) have the capability to target and kill specific-pathogens on illumination with visible light, without affecting the growth of other cells. While the growth of selected cells and the targeted pathogens is unaffected in dark, we selectively designed different LARS species which can either kill or proliferate the growth of selected target cells. This is demonstrated when targeting Escherichia coli cells, HEK293 mammalian cells, as well as, a co-culture of E. coli and HEK293 cells. Furthermore, within the same strain of E.coli, we find that while lab strain DH5α is susceptible to LARS, clinically isolated multi-drug resistant clinical strain of E. coli is not; likely due to presence of a non-specific antibiotic resistance mechanism. The ability to tune the biochemical potential of nanoparticles allows for selective cell phenotypes over a range of organisms, and has potential applications in antimicrobials and targeted organism-specific therapeutics.