Date of Award

Spring 1-1-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Prashant Nagpal

Second Advisor

Anushree Chatterjee

Third Advisor

Joel Kaar

Fourth Advisor

Jeffrey Cameron

Fifth Advisor

Wei Zhang

Abstract

Due to extensive use of antibiotics various strains multidrug resistant bacteria are emerging rapidly. In USA alone according to CDC report 2013 more than 2 million is affected by these strains of multidrug resistant bacteria causing several deaths. Hence an effective way of diagnostics and therapeutics need to be designed which can successfully combat the menace of

multidrug drug resistant bacteria.

In the present thesis, we discuss about novel strategies for both diagnostics and therapeutics for multidrug resistant bacteria. In the 1st chapter we discuss a novel DNA sequencing technique utilizing purely optical spectroscopy techniques like surface enhanced Raman and FTIR spectroscopy using 3D plasmonic nano focusing. This technique can be effective in doing single molecular study, detecting any mutations or epigenetic influences that can result in development of multi drug resistance in bacteria. In the 2nd chapter we show that among different ROS, only superoxide was found to be bactericidal, killing a range of multidrug-resistant (MDR) pathogens without affecting the viability or growth of mammalian cells. In our in vitro studies, intracellular superoxide generation using light-activated quantum dots yielded highly selective and effective antimicrobial action. These results can pave the way for rational design of nanoscale therapies as precision medicine.

In the 3rd chapter we show the design of superoxide-generating QDs using optimal QD material and size well-matched to superoxide redox potential, negatively charged ligands to modulate their uptake in cells and selective redox interventions, and core/shell structures to improve their stability for therapeutic action.

In the 4th chapter we discuss about alloy quantum dots lowering cadmium content and replacing it with more benign zinc content. Using QDs with low cadmium content as alternative candidates for selective light-activated therapy, we show negligible toxicity of these QDs to mammalian cells, while maintaining high treatment efficacy against MDR pathogens. These results provide design principles for developing different QDs as selective therapeutics to counter the growing threat of antimicrobial resistant infections.

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