Full metadata
Title
Aminoglycosides-derived Lipopolymer Nanoparticles for Delivery of mRNA
Description
The use of mRNA for therapeutic purposes has gained significant attention due to its potential to treat a wide range of diseases, including cancer, infectious diseases, and genetic disorders. However, the efficient delivery of mRNA to target cells remains a major challenge, and delivery of mRNA faces major issues such as rapid degradation and poor cellular uptake. Aminoglycoside-derived lipopolymer nanoparticles (LPNs) have been shown as a promising platform for plasmid DNA (pDNA) delivery due to their stability, biocompatibility, and ability to encapsulate mRNA. The current study aims to develop and optimize LPNs formulation for the delivery of mRNA in aggressive cancer cells, using a combination of chemical synthesis, physicochemical characterization, and in vitro biological assays. From a small library of aminoglycoside-derived lipopolymers, the lead lipopolymers were screened for the efficient delivery of mRNA. The complexes were synthesized with different ratios of lipopolymers to mRNA. The appropriate binding ratios of lipopolymers and mRNA were determined by gel electrophoresis. The complexes were characterized using dynamic light scattering (DLS) and zeta potential. The transgene expression efficacy of polymers was evaluated using in vitro bioluminescence assay. The toxicity of LPNs and LPNs-mRNA complexes was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The current study comprehensively investigates the optimization of the LPNs-mRNA formulation for enhanced efficacy in transgene expression in human advanced-stage melanoma cell lines.
Date Created
2023
Contributors
- Wubhayavedantapuram, Revanth (Author)
- Rege, Kaushal (Thesis advisor)
- Acharya, Abhinav (Committee member)
- Yaron, Jordan (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
55 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.2.N.187385
Level of coding
minimal
Cataloging Standards
Note
Partial requirement for: M.S., Arizona State University, 2023
Field of study: Chemical Engineering
System Created
- 2023-06-06 07:28:47
System Modified
- 2023-06-06 07:28:51
- 1 year 5 months ago
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