Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics
<p>Cancer is one of the major causes of mortality nowadays, owing to the lack of accurate diagnostic and therapeutic techniques. DNA-based nanomaterials show extraordinary performance in cancer diagnosis and have applications in therapy, owing to their predictable secondary structures, small s...
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| Format: | Thesis |
| Language: | English |
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2021
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| _version_ | 1826309705165701120 |
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| author | Yuan, L |
| author2 | Brown, T |
| author_facet | Brown, T Yuan, L |
| author_sort | Yuan, L |
| collection | OXFORD |
| description | <p>Cancer is one of the major causes of mortality nowadays, owing to the lack of accurate diagnostic and therapeutic techniques. DNA-based nanomaterials show extraordinary performance in cancer diagnosis and have applications in therapy, owing to their predictable secondary structures, small sizes, excellent biocompatibility, and programmability.</p>
<p>Rolling circle amplification (RCA) has been identified as a promising technique to make DNA nanomaterials, including DNA hydrogels, origami, nanoribbons, nano scaffolds and DNA nanoflowers (DNFs). These DNA nanomaterials have potential in a wide variety of applications, involving drug delivery, in vivo imaging, electronic circuit fabrication and therapeutics. However, there was a lack of chemistry to expand their functionality, which greatly limited their applications. To address this, we developed a strategy involving commercially available modified nucleoside triphosphates in RCA, resulting in densely modified products. The modified RCA products can then be functionalised by targeting moieties such as aptamer and peptide, which enhance their binding ability towards specific cancer cells.</p>
<p>The size of the RCA generated particles can be tuned through reaction time, Mg2+ concentration and the addition of polymers such as PLL and PEG. The PEGylated products can be labelled using the abovementioned method, leading to condensed fluorescent particles with better cellular uptake.</p>
<p>Additionally, a nanocarrier system based on cyclic DNA was designed and evaluated for mRNA detection in cells. The untemplated cyclisation of DNA through CuAAC chemistry was efficient, and the multivalent system showed an improved binding towards target cancer cells. However, the internalisation of the system by cells needs to be improved. Entrapment of the system in subcellular compartments was observed, which significantly increased the background signal.</p> |
| first_indexed | 2024-03-07T07:39:42Z |
| format | Thesis |
| id | oxford-uuid:ac1ee51b-1b39-4761-9bad-836656e1e189 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:39:42Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | oxford-uuid:ac1ee51b-1b39-4761-9bad-836656e1e1892023-04-12T11:51:40ZDesign of multivalent DNA nanomaterials for use in cancer diagnostics and therapeuticsThesishttp://purl.org/coar/resource_type/c_db06uuid:ac1ee51b-1b39-4761-9bad-836656e1e189Nucleic acidsEnglishHyrax Deposit2021Yuan, LBrown, THollenstein, MWilliams, A<p>Cancer is one of the major causes of mortality nowadays, owing to the lack of accurate diagnostic and therapeutic techniques. DNA-based nanomaterials show extraordinary performance in cancer diagnosis and have applications in therapy, owing to their predictable secondary structures, small sizes, excellent biocompatibility, and programmability.</p> <p>Rolling circle amplification (RCA) has been identified as a promising technique to make DNA nanomaterials, including DNA hydrogels, origami, nanoribbons, nano scaffolds and DNA nanoflowers (DNFs). These DNA nanomaterials have potential in a wide variety of applications, involving drug delivery, in vivo imaging, electronic circuit fabrication and therapeutics. However, there was a lack of chemistry to expand their functionality, which greatly limited their applications. To address this, we developed a strategy involving commercially available modified nucleoside triphosphates in RCA, resulting in densely modified products. The modified RCA products can then be functionalised by targeting moieties such as aptamer and peptide, which enhance their binding ability towards specific cancer cells.</p> <p>The size of the RCA generated particles can be tuned through reaction time, Mg2+ concentration and the addition of polymers such as PLL and PEG. The PEGylated products can be labelled using the abovementioned method, leading to condensed fluorescent particles with better cellular uptake.</p> <p>Additionally, a nanocarrier system based on cyclic DNA was designed and evaluated for mRNA detection in cells. The untemplated cyclisation of DNA through CuAAC chemistry was efficient, and the multivalent system showed an improved binding towards target cancer cells. However, the internalisation of the system by cells needs to be improved. Entrapment of the system in subcellular compartments was observed, which significantly increased the background signal.</p> |
| spellingShingle | Nucleic acids Yuan, L Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics |
| title | Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics |
| title_full | Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics |
| title_fullStr | Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics |
| title_full_unstemmed | Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics |
| title_short | Design of multivalent DNA nanomaterials for use in cancer diagnostics and therapeutics |
| title_sort | design of multivalent dna nanomaterials for use in cancer diagnostics and therapeutics |
| topic | Nucleic acids |
| work_keys_str_mv | AT yuanl designofmultivalentdnananomaterialsforuseincancerdiagnosticsandtherapeutics |