Investigating DNA−polymer conjugates by low-volume aqueous polymerization-induced self-assembly (PISA)

Chaimueangchuen, Siriporn ORCID: 0000-0001-7932-3125 (2024). Investigating DNA−polymer conjugates by low-volume aqueous polymerization-induced self-assembly (PISA). University of Birmingham. Ph.D.

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Abstract

Over the past few decades, deoxyribonucleic acid (DNA)-polymer conjugates have been attracting interest as adaptable functional materials in various biorelated applications. However, determining the optimal synthetic conditions of conjugating hydrophilic DNA with hydrophobic polymers still presents a significant challenge and this limitation currently constrains the progress of research in this field. In recent decades, polymerization-induced self-assembly (PISA) has attracted significant attention for constructing nano-objects with various morphologies such as vesicles, worms, and spheres owing to the one-step nature of the process. To date, the most commonly utilized polymerization technique in PISA is reversible-addition fragmentation chain transfer (RAFT) polymerization due to its versatility and broad applicability.1, 2 In RAFTmediated emulsion PISA, a solvophilic macromolecular chain transfer agent (macroCTA) and a solvent-miscible monomer are polymerized to generate solvophobic polymer and create self-assembled nanostructures.3 Thus, PISA could be a potential method for producing amphiphilic DNA-polymer nanostructures. However, the high cost of DNA necessitates the use of minimal reaction volumes in PISA procedures, which remains an
ongoing challenge due to limitations such as oxygen inhibition, low potential reproducibility, and the requirement for special equipment. This Ph.D. project aims to develop reproducible conditions for low-volume PISA reactions in an attempt to utilize a deoxyribonucleic acid macromolecular chain transfer agent (DNA-macroCTA) and 2- hydroxypropyl methacrylate (HPMA) monomer to generate DNA-decorated polymeric nanostructures of various morphologies via PISA for future medical applications.In chapter 2, poly(ethylene glycol) macromolecular chain transfer agent was synthesized, and their corresponding synthetic diblock copolymers with HPMA monomer were prepared via RAFT-mediated photoinitiated PISA. The optimalization of a low-volume system was investigated through physical and chemical strategies to eliminate oxygen
inhibition in low-volume polymerization. Nitrogen glove bag method was applied for curing in an oxygen-free atmosphere for physical strategy while glucose oxidase (GOx) in the presence of glucose, was applied in chemical strategy. Moreover, phase diagram was investigated in the optimal low volume conditions. This optimal low volume condition was applied with the DNA-macroCTA and the identical HPMA monomer in
chapter 3. This chapter was divided into two sections, each focusing on the generation of DNA-PHPMA nanoparticles through different sources of synthesized DNA-macroCTA. The first section utilized DNA-macroCTA received from the Sleiman group, our collaborators while the second section involved DNA-macroCTA synthesized by our group. Additionally, two methods for synthesizing DNA-macroCTA were highlighted, involving both solution-based and solid support approaches. This chapter further explored the impact of salts and hybridization with the DNA-polymer particles. In chapter 4, the combination of PEG-macroCTA and DNA-macroCTA was investigated to facilitate morphological transitions in DNA-decorated particles. Moreover, the utilization of hybridization and hybridization chain reaction (HCR) was explored with the mixture corona of PEG and DNA.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):