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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

<b>ELASTIN-LIKE POLYPEPTIDE: A BIOPOLYMER WITH DIVERSE APPLICATIONS IN HEMICAL/BIOLOGICAL STUDIES</b>

Saloni Darji (13514293) 04 March 2025 (has links)
<p dir="ltr">Elastin-like polypeptides are one class of synthetic or naturally derived polymers that have properties tropoelastin, an abundant protein present in the skin. ELPs have a peculiar pentapeptide repeat sequence allows it to undergo reversible phase transition upon changing temperature. ELPs also have excellent biocompatibility and bioengineering ability making it suitable for a wide range of biomedical, therapeutic and other chemical applications. Therefore, this thesis focuses on the potential of ELPs across various applications-most importantly in the areas of biocatalysis, bladder cancer detection, and gene delivery. In the context of the former application, related to biocatalysis, ELP-enzyme fusion, a cleavable ELP-Intein construct fused with chorismite mutase (ELP−I-Cm2)-has been utilized as a model to understand its behavior in organic phase. Hydrophobic nature of ELPs, allowed ELPs to stabilize in the organic phase, and phase separate from other contaminants. Further, enzyme activity was detected post phase separation, and a secondary structure was retained in this process. Further investigation indicated a reverse micellar structure formation allowing enzyme stability in organic phase also allowing reverse micellar catalysis. In the realm of tumor detection, an NIR imaging agent was designed via the conjugation of EGF with ELP to detect bladder cancer cells expressing high levels of EGFR. The agent, with the name Cy5.5-N24-EGF, showed excellent specificity and sensitivity, effectively distinguishing tumor tissue from normal adjacent tissues in both human and canine models. Flow cytometry and confocal microscopy confirmed selective engagement of EGFR-positive cells by the probe, which therefore has great potential for clinical translation into diagnostics in bladder cancer. Finally, ELPs represent a modern formulation approach to gene delivery in the treatment of bladder cancer using layer-by-layer ELP nucleic acid nanoparticles (LENN). This system demonstrated high versatility in delivering mRNA, utilizing clathrin-mediated endocytosis mainly for internalization. Accordingly, LENN provided improved stability and encapsulation efficiency, thus representing a promising alternative both to conventional viral vectors and to lipid-based systems for gene therapy applications with improved efficacy. Together, these applications illustrate the various ways in which ELPs may contribute to the development of novel chemical and biomedical research and therapeutic strategies.</p>

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