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Nanoparticle-DNA conjugates for biomedical applications

Nanoparticle-DNA conjugates for biomedical applications
Nanoparticle-DNA conjugates for biomedical applications
In recent years biomolecules have been used to infer specific functionality to nanomaterials. Advances in conjugation techniques have allowed for the development of a vast range of hybrid bio-nano materials. Their applications range from biosensing and targeted therapy to metamaterials. In particular the conjugation of nanomaterials to functional oligonucleotides has been a thriving area of scientific research.

In this project the main aim was to explore the uses of gold nanoparticle-DNA conjugates for biomedical applications. Probes for the real-time intracellular detection of mRNA were synthesized. These probes showed great target specificity, excellent biocompatibility and good cellular uptake. Importantly, unlike free nucleic acids, they displayed no susceptibility to degradation by nuclease enzymes. The ability to detect mRNAs in a live cell, in real time has tremendous diagnostic applications.

Furthermore, multifunctional probes were designed. In addition to live cell mRNA detection, we developed probes with the ability to deliver a cytotoxic drug. Utilizing their inherent high specificity for target mRNAs, we demonstrated that cell-type specific targeted drug delivery was possible. In the absence of the target mRNA, the drug remained tightly bound within the probe.

With a view of developing advanced materials, capable of performing multiple roles simultaneously, we investigated the use of nanoparticle assemblies for biomedical applications. In order to create highly stable nanoconstructs, a novel tool for the programmed assembly of DNA-nanomaterials was demonstrated. The use of copper-free click chemistry resulted in nano-assemblies connected by ssDNA. The employment of this novel tool proved to produce assemblies with covalently linked particles. Moreover, it was shown that gold nanoparticle dimers displayed excellent stability with respect to a variety of conditions commonly met within a biological environment.

Additionally, the formation of heterogeneous nanoassemblies was demonstrated. Dimers of optical and either semi-conductor or magnetic nanocrystals were assembled representing examples of multi-role probes with exciting potential for applications in biomedicine.
University of Southampton
Heuer-Jungmann, Amelie
48f01a95-9ba4-4248-bd24-0e20d601d2cc
Heuer-Jungmann, Amelie
48f01a95-9ba4-4248-bd24-0e20d601d2cc
Kanaras, Antonios G.
667ecfdc-7647-4bd8-be03-a47bf32504c7

Heuer-Jungmann, Amelie (2014) Nanoparticle-DNA conjugates for biomedical applications. University of Southampton, Physical Sciences and Engineering, Doctoral Thesis, 241pp.

Record type: Thesis (Doctoral)

Abstract

In recent years biomolecules have been used to infer specific functionality to nanomaterials. Advances in conjugation techniques have allowed for the development of a vast range of hybrid bio-nano materials. Their applications range from biosensing and targeted therapy to metamaterials. In particular the conjugation of nanomaterials to functional oligonucleotides has been a thriving area of scientific research.

In this project the main aim was to explore the uses of gold nanoparticle-DNA conjugates for biomedical applications. Probes for the real-time intracellular detection of mRNA were synthesized. These probes showed great target specificity, excellent biocompatibility and good cellular uptake. Importantly, unlike free nucleic acids, they displayed no susceptibility to degradation by nuclease enzymes. The ability to detect mRNAs in a live cell, in real time has tremendous diagnostic applications.

Furthermore, multifunctional probes were designed. In addition to live cell mRNA detection, we developed probes with the ability to deliver a cytotoxic drug. Utilizing their inherent high specificity for target mRNAs, we demonstrated that cell-type specific targeted drug delivery was possible. In the absence of the target mRNA, the drug remained tightly bound within the probe.

With a view of developing advanced materials, capable of performing multiple roles simultaneously, we investigated the use of nanoparticle assemblies for biomedical applications. In order to create highly stable nanoconstructs, a novel tool for the programmed assembly of DNA-nanomaterials was demonstrated. The use of copper-free click chemistry resulted in nano-assemblies connected by ssDNA. The employment of this novel tool proved to produce assemblies with covalently linked particles. Moreover, it was shown that gold nanoparticle dimers displayed excellent stability with respect to a variety of conditions commonly met within a biological environment.

Additionally, the formation of heterogeneous nanoassemblies was demonstrated. Dimers of optical and either semi-conductor or magnetic nanocrystals were assembled representing examples of multi-role probes with exciting potential for applications in biomedicine.

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More information

Published date: December 2014
Organisations: University of Southampton, Quantum, Light & Matter Group

Identifiers

Local EPrints ID: 374319
URI: http://eprints.soton.ac.uk/id/eprint/374319
PURE UUID: 2e33fa83-f275-43dd-99b0-348d56e6f10c
ORCID for Antonios G. Kanaras: ORCID iD orcid.org/0000-0002-9847-6706

Catalogue record

Date deposited: 16 Feb 2015 14:42
Last modified: 15 Mar 2024 05:13

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Contributors

Author: Amelie Heuer-Jungmann
Thesis advisor: Antonios G. Kanaras ORCID iD

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