Sankaran ThayumanavanWu, Peidong2024-04-262024-04-262023-022023-0210.7275/31645471https://hdl.handle.net/20.500.14394/19156Delivery of therapeutics specifically to the disease site is the final goal for the field of drug discovery. Considerable efforts in understanding disease biology have contributed to identifying novel therapeutics such as small molecules, proteolysis targeting chimeras (PROTACs), peptides, proteins, and nucleic acids. However, improving their efficacy as well as minimizing their off-target toxicity remains challenging. Developing vectors that could not only efficiently encapsulate these therapeutics but also direct these therapeutics to the target site is a potential solution to address these challenges. In this dissertation, a block-copolymer-based nanoparticle platform has been developed optimized, and decorated with various kinds of ligands to explore multiple applications, viz., i) stable encapsulation and tunable release kinetics of hydrophobic drug molecules; ii) multiplexed sensing of the cellular uptake of functional nanoparticles; iii) understanding the relationship between surface decorated ligands and their performance during cellular uptake, transcytosis processes in endothelial cells and tumor penetration process; iv) developing and optimizing antibody nanoparticle conjugate (ANC) for cell-specific delivery of drugs; v) explore the delivery of PROTAC with different linkers in nanoparticle formulation. The work in this dissertation demonstrated a nanoparticle platform with several merits: i) ease of preparation; ii) low cytotoxicity; iii) addressable surface properties; iv) stable drug encapsulation; v) redox responsive release of encapsulated cargos. The comparison between antibody-drug conjugate and ANC reveals the potential of ANC as a promising next-generation nanomedicine. Note, that this platform can further be translated to target various types of disease tissues with other novel therapeutics encapsulated.Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/polymernanoparticledrug deliveryChemistryDissertation (Open Access)https://orcid.org/0000-0002-8655-0761