Physical Properties of Model Drug Carriers Dictate Their Internalization Efficiency via Clathrin-Mediated Endocytosis
Transmembrane receptors expressed at the cell surface modulate nutrient uptake and facilitate cellular signaling. To enable the cell to respond to external stimuli, these processes are dynamic and often require receptor recycling via endocytosis. A popular strategy for therapeutic delivery to cells...
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| Main Author: | |
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| Format: | Dissertation |
| Language: | English |
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ProQuest Dissertations & Theses
01-01-2024
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| Online Access: | Get full text |
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| Summary: | Transmembrane receptors expressed at the cell surface modulate nutrient uptake and facilitate cellular signaling. To enable the cell to respond to external stimuli, these processes are dynamic and often require receptor recycling via endocytosis. A popular strategy for therapeutic delivery to cells and tissues is to encapsulate therapeutics inside particles that are conjugated with ligands that correspond to transmembrane receptors expressed at the cellular surface and are internalized by endocytic pathways. There are multiple routes of internalization that can be targeted, but the most well-understood process is clathrin-mediated endocytosis. In targeted therapeutic delivery, the efficacy of particle uptake is often characterized by flow cytometry and Western blot assays. However, these techniques do not inform on the detailed mechanisms of particle uptake. To address this gap, I employed a live-cell imaging technique to study individual particle uptake events that interact with clathrin-coated structures. This analysis can elucidate the dynamic interactions between individual drug-carriers and endocytic structures, which influences the probability of particle internalization. Leveraging this technique, I probe into how ligand density, particle size, and particle stiffness can influence the probability of uptake. My findings provide guidance on previously unexplored aspects of targeted delivery that could be leveraged to design more effective therapeutic carriers. |
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| ISBN: | 9798384440703 |