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Development of Nanoparticle-based Platforms for Potential Applications in Biosensing and Therapeutics

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2017, PhD, University of Cincinnati, Arts and Sciences: Chemistry.
In this dissertation, I first developed and optimize an upconversion nanoparticles-based DNA detection scheme on different target DNA sequences, and then I explored the syntheses and characterizations of a nanomaterial-photosensitizer platform used for photodynamic therapy of cancer cells and bacteria in vitro. In the first project, a novel ligase-assisted signal-amplifiable DNA detection scheme is demonstrated based on luminescent resonance energy transfer between upconversion nanoparticles and the intercalating dye, SYBR Green I. Target DNA serves as a template for two DNA probes, one of them covalently attached to upconversion nanoparticles, to be joined into a long, hairpin-forming DNA by ligase. The number of the resulting DNA strand, which brings SYBR Green I close to the upconversion nanoparticles, is amplified through thermal cycling. The method was proven to display high sensitivity and specificity for DNA detection. Factors affecting the detection specificity and sensitivity, including ligation temperature, the amount of ligase, and the number of thermal cycles, have been investigated to optimize the performance of the detection method. Based on our result, the detection scheme can easily differentiate the BRAF V600E mutation from the wild-type sequence with a mutant-to-wild-type ratio of 1:1000. A detection limit of 1 fmole BRAF V600E mutation is achieved. While for the target sequence of EGFR T790M, the differentiate ratio is 1:100. The results show that 0.01 pmole of EGFR T790M mutant can be readily detected. In the second project, I report a hybrid singlet oxygen production system, where strong resonance coupling between silver nanoparticles and photosensitizing molecules results in exceptionally high singlet oxygen production under both visible light and near-infrared light excitation, even for the photosensitizing molecules without near-infrared absorption. Also, our results indicate that the hybrid photosensitizers display low cytotoxicity without light illumination yet highly enhanced photodynamic inhibition efficacy against Hela cells under a broad spectrum of light illuminations including the near-infrared light, which has great implication in photodynamic therapy of deep-tissue cancers. In addition, formulation of hybrid photosensitizers dispersed in PEG matrix demonstrates high bacterial killing efficacy against both S. epidermidis and P. acnes, suggesting it has immense potential for treatment of acne vulgaris without involving antibiotics.
Peng Zhang, Ph.D. (Committee Chair)
William Heineman, Ph.D. (Committee Member)
Pearl Tsang, Ph.D. (Committee Member)
132 p.

Recommended Citations

Citations

  • Wang, P. (2017). Development of Nanoparticle-based Platforms for Potential Applications in Biosensing and Therapeutics [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin151186771296011

    APA Style (7th edition)

  • Wang, Peng. Development of Nanoparticle-based Platforms for Potential Applications in Biosensing and Therapeutics. 2017. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin151186771296011.

    MLA Style (8th edition)

  • Wang, Peng. "Development of Nanoparticle-based Platforms for Potential Applications in Biosensing and Therapeutics." Doctoral dissertation, University of Cincinnati, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin151186771296011

    Chicago Manual of Style (17th edition)