자료유형  

 학위논문

Control Number  

0017163759

International Standard Book Number  

9798342113854

Dewey Decimal Classification Number  

600

Main Entry-Personal Name  

Sun, Jiuzhi.

Publication, Distribution, etc. (Imprint  

[S.l.] : Stanford University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

452 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-04, Section: B.

General Note  

Advisor: Wender, Paul.

Dissertation Note  

Thesis (Ph.D.)--Stanford University, 2024.

Summary, Etc.  

요약Biological barriers are fundamental to all living systems. As a result, all therapeutic agents, imaging agents and probes must navigate through various membrane barriers, such as cell membranes, the blood-retinal barrier, the blood-brain barrier, and the skin barrier, to effectively reach their intended targets. Breaching these biological barriers is particularly critical in the realm of precision medicine, where the design and preparation of effective carriers for drugs and diagnostic agents are vital to ensure that the drug is well-protected, precisely targeted, less toxic, and more effective. Non-specific delivery of therapeutic molecules can lead to issues such as low selectivity, increased toxicity, and the potential for drug resistance. Therefore, innovative physical, chemical, and biological methods are being developed to penetrate the protective barriers, enabling therapeutic molecules to maintain their effectiveness and exert their therapeutic effects. The overarching aim of our research in Wender lab is to establish new, efficient drug delivery systems for potential clinical translation. By exploring different delivery methods, utilizing both covalent conjugation or non-covalent complexation of the therapetic agents and their carriers, we strive to overcome the limitations posed by biological barriers.The research projects that I have worked on can be broadly classified into two categories, each addressing a unique aspect of drug delivery challenges. The first category focuses on the development of innovative Charge-Altering Releasable Transporters (CARTs) for mRNA delivery. This cuttingedge approach has significant implications for a variety of biomedical applications. By harnessing the capabilities of CARTs to enable efficient delivery of mRNA, we provide innovative solutions for immune cell engineering and vaccine formulation. The second category of our projects is centered on the development of novel dual-function molecular transporter-antibiotic conjugates. This initiative is specifically designed to address the challenge posed by multi-drug-resistant pathogens. By merging the transporter and antibiotic into a single conjugate, our strategy is designed to combat these resistant pathogens, ensuring a more effective penetration and action of the antibiotic. This dualfunctionality approach opens new avenues in the fight against antibiotic resistance. Together, these two categories of research represent our commitment to advancing the frontiers of drug delivery technology, with the ultimate goal of addressing some of the unmet needs in modern medicine.In the opening chapter, we delve into the remarkable advancements in drug delivery systems that have effectively translated innovative therapeutic concepts into viable, FDA-approved clinical treatments. As the pharmaceutical industry evolves from the realm of small-molecule drugs to the more complex biological entities, innovative delivery platforms have emerged as critical enabling technologies that facilitate the broad implementation and rapid translation of novel therapeutics. These systems are often designed to optimize pharmacokinetic profiles, enhance the targeting precision and improve safety profiles. Specifically, this chapter will highlight significant milestones in the field, review successful, FDA-approved delivery systems, and discuss the promising future of emerging drug delivery technologies.Next, we delve into glycerol-based Charge-Altering Releasable Transporters (CARTs) for CARNK cell engineering. This section of the thesis discusses the development of glycerol CARTs, designed for efficient transfection across a range of cell types, including immortalized immune cells, peripheral blood mononuclear cells (PBMCs), and importantly, human primary NK cells. Our research highlights the potential of glycerol CARTs in NK cell engineering using a one-component system for mRNA delivery. We provide evidence of successful transfection of primary NK cells with anti-HIV CAR-encoding mRNA, which leads to the expression of CAR on NK cell surfaces and the subsequent activation of NK cells in the presence of HIV-infected CD4+ T cells. Our results demonstrate that glycerol CARTs are effective tools for NK cell engineering, showing promise for various ex vivo biomedical applications. I would like to extend my sincere gratitude to Ruoxi Pi and Harrison Rahn for their invaluable contributions and collaboration in this segment of research.

Subject Added Entry-Topical Term  

Pathogens.

Subject Added Entry-Topical Term  

Glycerol.

Subject Added Entry-Topical Term  

Toxicity.

Subject Added Entry-Topical Term  

Biofilms.

Subject Added Entry-Topical Term  

Nanoparticles.

Subject Added Entry-Topical Term  

Cytotoxicity.

Subject Added Entry-Topical Term  

Antibiotics.

Subject Added Entry-Topical Term  

Personal development.

Subject Added Entry-Topical Term  

E coli.

Subject Added Entry-Topical Term  

Lipids.

Subject Added Entry-Topical Term  

Drug dosages.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Microbiology.

Subject Added Entry-Topical Term  

Nanotechnology.

Subject Added Entry-Topical Term  

Pharmaceutical sciences.

Subject Added Entry-Topical Term  

Toxicology.

Added Entry-Corporate Name  

Stanford University.

Host Item Entry  

Dissertations Abstracts International. 86-04B.

Electronic Location and Access  

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Control Number  

joongbu:655056