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Dissertation document_Weiyu Zhao.pdf (2.59 MB)

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Development of Functionalized Biomaterials for Biomedical Applications

Zhao, Weiyu
http://rave.ohiolink.edu/etdc/view?acc_num=osu1594988786199951

Abstract Details

2020, Doctor of Philosophy, Ohio State University, Pharmacy.
Functionalized biomaterials play essential roles in achieving effective delivery of diagnostic or therapeutic agents. These functionalized materials, incorporated with superior properties, suchlike tissue-targeting or stimuli-responsive, could contribute to the implementation of accurate detections on diseases and the maximization of therapeutic windows for disease treatments. Some examples of the functionalized biomaterials include, but not limit to, bio-responsive fluorescent imaging probes, which are capable of sensing the molecular analytes in the biological systems and thus enable a more sensitive detection of disease; antibody drug conjugates (ADCs), which integrate the specificity of antibodies with the potency of cytotoxic agents, and may install with cleavable linkers for controlled release of the payload at diseased sites; biodegradable and biocompatible lipid nanomaterials and lipid polymer hybrid nanomaterials, which enable potent delivery of payload molecules while maintaining good tolerability and safety. The objective of this dissertation is to develop functionalized biomaterials for biomedical applications. Chapter 2 disclosed a series of ratiometric fluorescent probes (ClO1-ClO6) for the detection of the endogenous hypochlorous acid (HClO). Among them, ClO1 probe, with one n-octadecane chain and two 2-[[2-(dimethylamino)ethyl]methylamino]-ethyl groups, was identified as a superior probe to target the lungs over other major organs in mice. In a lipopolysaccharide (LPS)-induced lung inflammation mouse model, ClO1 effectively captured endogenous HClO in the lungs of mice after intravenous administration. Chapter 3 described the design and synthesis of an antibody drug conjugate (ADC), named as CD123-CPT, which combined an anti-CD123 antibody with a chemotherapeutic agent, Camptothecin (CPT), via a disulfide linker. The established anti-CD123-CPT ADCs demonstrated potent inhibitory effects on CD123-overexpressed acute myeloid leukemia (AML) cells and a successful drug release in the presence of glutathione (GSH), an intracellular molecule that is highly expressed in cancer cells. Chapter 4 demonstrated a study on developing lipid polymer hybrid nanoparticles (LPNs) for mRNA delivery, where a series of biodegradable and biocompatible polymer materials were incorporated into a previously reported lead formulation, TT3-LLNs. Through screenings on mRNA delivery and a subsequent orthogonal optimization, PLGA4 was found to dramatically increase delivery efficiency of TT3-LLNs in comparison to other polymers, and PLGA4-7 LPNs were identified as a lead LPN formulation, which displayed significantly enhanced delivery of mRNA molecules in three different human cell lines as compared with TT3-LLNs. In summary, these functionalized biomaterials are promising tools for biomedical applications and worth further exploration for diagnostic as well as therapeutic purposes in the clinics.
Yizhou Dong (Advisor)
Mitch Phelps (Committee Member)
Peixuan Guo (Committee Member)
Navjot Pabla (Committee Member)
123 p.
Pharmaceuticals; Pharmacy Sciences

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Citations

  • Zhao, W. (2020). Development of Functionalized Biomaterials for Biomedical Applications [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1594988786199951

    APA Style (7th edition)

  • Zhao, Weiyu. Development of Functionalized Biomaterials for Biomedical Applications. 2020. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1594988786199951.

    MLA Style (8th edition)

  • Zhao, Weiyu. "Development of Functionalized Biomaterials for Biomedical Applications." Doctoral dissertation, Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1594988786199951

    Chicago Manual of Style (17th edition)

osu1594988786199951
128
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This open access ETD is published by The Ohio State University and OhioLINK.