Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

Functional Conjugates for Drug and Gene Delivery

Zhang, Chengxiang
http://rave.ohiolink.edu/etdc/view?acc_num=osu158703024326976

Abstract Details

2020, Doctor of Philosophy, Ohio State University, Pharmaceutical Sciences.
Efficient drug delivery enhances the safety and efficacy of drug product. However, the physicochemical characteristics of drug molecule and physiological properties of biological barriers may reduce the drug delivery efficiency and limit the drug application. For example, the hydrophobic drug may need to be dissolved in excipient with potential toxicity to increase water solubility. Drugs with low cell permeability cannot reach cytosol and may lose their therapeutic efficacy. Moreover, the off target of drug may induce sever side effect and systemic toxicity. The objective of this dissertation is to improve drug and gene delivery by using functional conjugates as targeted drug delivery platform and material building blocks of drug delivery system. In chapter 2, we designed and synthesized Dara-DM4, an antibody drug conjugate (ADC), by conjugating Daratumumab and DM4 via a disulfide linker. Dara-DM4 showed significantly higher cellular uptake and targeted inhibitory efficacy on multiple myeloma cancer cells that overexpressing CD38. In chapter 3, we synthesized penicillin G-derived lipid conjugates, PenG-PL. Then, we formulated the drug-lipid conjugates into lipid nanoparticles. We found that penicillin G derived phospholipid nanoparticles (PenG-PL NPs) were able to enhance cellular uptake of penicillin G as compared with free penicillin G and eliminate intracellular methicillin sensitive Staphylococcus aureus (S. aureus) in infected cells. In chapter 4, we synthesized paclitaxel derived amino lipid, PAL. Then, we formulated the drug-lipid conjugates with P53 mRNA to afford PAL P53 mRNA nanoparticles (NPs). PAL P53 mRNA NPs increased the water solubility of paclitaxel. In addition, the NPs delivered paclitaxel and P53 mRNA into cells and displayed synergetic cytotoxicity of the two types of components in cultured triple-negative breast cancer cells. We also demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. In summary, functional conjugates represent useful tools for improving drug and gene delivery and merit further development for therapeutic applications.
Yizhou Dong (Advisor)
Peixuan Guo (Committee Member)
Robert Lee (Committee Member)
Mitch Phelps (Committee Member)
118 p.
Pharmaceuticals

Recommended Citations

Citations

  • Zhang, C. (2020). Functional Conjugates for Drug and Gene Delivery [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu158703024326976

    APA Style (7th edition)

  • Zhang, Chengxiang. Functional Conjugates for Drug and Gene Delivery. 2020. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu158703024326976.

    MLA Style (8th edition)

  • Zhang, Chengxiang. "Functional Conjugates for Drug and Gene Delivery." Doctoral dissertation, Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu158703024326976

    Chicago Manual of Style (17th edition)

osu158703024326976
200
© 2020, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.