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Controlling Reactivity and Triggerability Using Intramolecular and Ad Hoc Electrostatic Interactions

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Abstract
Electrostatic interactions play a vital role in natural design principles. An extraordinary amount of impact of such interactions also can be observed in evolutionary biology. The profound impact of these interactive forces underscores their pivotal role, yet there remains ample scope to develop our grasp of the bases that regulate and manipulate these interactions. Enriched intellectual capacity regarding electrostatic interactions will enable their more sophisticated and effective application across diverse platforms, unlocking new avenues and innovations. This dissertation reviews charge-based interactions at the molecular level and presents three perspectives on their fundamental and practical applications. The dissertation focuses on three key aspects i) studying intramolecular electrostatic interactions in tertiary amine-based zwitterionic structures, showing how these interactions affect reaction kinetics and nanostructure formation ii) developing hybrid lipid-polymer nanoparticles for RNA delivery using a ‘de-cationizable’ non-viral design, highlighting the separate roles of encapsulation and intracellular trafficking in optimizing delivery vectors. It also creates a unique opportunity to impose targeted delivery capabilities for selective treatment of excruciating diseases like triple-negative breast cancer, using a two-factor authentication approach for enhanced selectivity and efficacy. iii) Additionally, the dissertation explores improving electroporation in T-cells with anionic polymers attached to targeting antibodies, aimed at enhancing targeted cell therapies. Finally, this thesis summarizes these findings and discusses prospects, emphasizing the multifaceted roles of electrostatic interactions in biomedical research.
Type
Dissertation (Open Access)
Date
2024-09
Publisher
License
Attribution 4.0 International
Attribution 4.0 International
License
http://creativecommons.org/licenses/by/4.0/
Research Projects
Organizational Units
Journal Issue
Embargo Lift Date
2025-09-01
Publisher Version
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