Multiple valency and assay amplification
Multiple valency and assay amplification
Six libraries of dendrimers were successfully synthesised using solid phase methodology. Three libraries were tested for cellular transfection activity and the cells analysed by flow cytometry. Twelve amphiphilic dendrimers displayed improved activity compared to Superfact and Effectene (commercial transfection agents) in transfecting HeLa cells and five components were found to be better or comparable to Superfect and Effectene in transfecting HEK293T and ND7 cells. The efficacy of transfection was dependent on the dendrimer generation, the structure of the compounds and the weight ratio of the complexes. In general the compounds were found to be non-toxic. A microarray approach aimed at the HTS of the dendrimeric compounds as efficient DNA delivery systems was demonstrated and the multiplexing capability of this new method was exploited by screening the libraries on a broad range of cells in a very rapid manner.
A library of dendritic chlorambucil compounds as alkylating agents was evaluated using an alkaline agarose gel assay. Among the twenty four compounds tested, eighteen compounds were able to cross-link DNA efficiently and the cross-linking was enhanced when the number of alkylating units was amplified. Ten of whose active compounds were more potent than chlorambucil against A20 and HeLa cells (IC50 values: 4-110 μM). Encouraging results on cellular uptake and toxicity studies (against HeLa and B16F10 cells) were shown by a library of photosensitisers (for PDT applications). Four dendrimeric compounds bearing either hematoporphyrin (HP), zinc protoporphyrin (ZnPP) of Cy5 units were more potent than the correspondent parent compound. Dendrimeric HP’s were the most efficient compounds, showing strong cellular uptake, enhanced fluorescent intensity and high phototoxicity but low dark toxicity against HeLa cells. Eight lactose conjugated dendrimers (glycodendrimers), targeting galectins for anti-cancer metastasis, were successfully synthesised by coupling lactosyl isothiocyanate to dendrimers, and three of the compounds were found to be active against MDA-MB231 cells.
University of Southampton
How, Siew-Eng
6e4f6a0f-a881-444b-8729-ab7ce6c013e7
2005
How, Siew-Eng
6e4f6a0f-a881-444b-8729-ab7ce6c013e7
How, Siew-Eng
(2005)
Multiple valency and assay amplification.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Six libraries of dendrimers were successfully synthesised using solid phase methodology. Three libraries were tested for cellular transfection activity and the cells analysed by flow cytometry. Twelve amphiphilic dendrimers displayed improved activity compared to Superfact and Effectene (commercial transfection agents) in transfecting HeLa cells and five components were found to be better or comparable to Superfect and Effectene in transfecting HEK293T and ND7 cells. The efficacy of transfection was dependent on the dendrimer generation, the structure of the compounds and the weight ratio of the complexes. In general the compounds were found to be non-toxic. A microarray approach aimed at the HTS of the dendrimeric compounds as efficient DNA delivery systems was demonstrated and the multiplexing capability of this new method was exploited by screening the libraries on a broad range of cells in a very rapid manner.
A library of dendritic chlorambucil compounds as alkylating agents was evaluated using an alkaline agarose gel assay. Among the twenty four compounds tested, eighteen compounds were able to cross-link DNA efficiently and the cross-linking was enhanced when the number of alkylating units was amplified. Ten of whose active compounds were more potent than chlorambucil against A20 and HeLa cells (IC50 values: 4-110 μM). Encouraging results on cellular uptake and toxicity studies (against HeLa and B16F10 cells) were shown by a library of photosensitisers (for PDT applications). Four dendrimeric compounds bearing either hematoporphyrin (HP), zinc protoporphyrin (ZnPP) of Cy5 units were more potent than the correspondent parent compound. Dendrimeric HP’s were the most efficient compounds, showing strong cellular uptake, enhanced fluorescent intensity and high phototoxicity but low dark toxicity against HeLa cells. Eight lactose conjugated dendrimers (glycodendrimers), targeting galectins for anti-cancer metastasis, were successfully synthesised by coupling lactosyl isothiocyanate to dendrimers, and three of the compounds were found to be active against MDA-MB231 cells.
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Published date: 2005
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Local EPrints ID: 465590
URI: http://eprints.soton.ac.uk/id/eprint/465590
PURE UUID: 670e2785-d4c7-4f54-ac5b-1c046677751a
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Date deposited: 05 Jul 2022 01:56
Last modified: 23 Jul 2022 02:16
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Author:
Siew-Eng How
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