Chudasama, V;
Bryden, F;
Savoie, H;
Maruani, A;
Cheng, M;
Beeby, A;
Rodrigues, J;
(2017)
Assembly of high-potency photosensitiser-antibody conjugates through application of dendron multiplier technology.
Bioconjugate Chemistry
, 29
(1)
pp. 176-181.
10.1021/acs.bioconjchem.7b00678.
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Abstract
Exploitation of photosensitisers as payloads for antibody-based anti-cancer therapeutics offers a novel alternative to the small pool of commonly-utilised cytotoxins. However, existing bioconjugation methodologies are incompatible with the requirement of increased antibody loading without compromising antibody function, stability or homogeneity. Herein, we describe the first application of dendritic multiplier groups to allow the loading of more than 4 porphyrins to a full IgG antibody in a site-specific and highly homogeneous manner. Photophysical evaluation of UV-visible absorbance and singlet oxygen quantum yields highlighted porphyrin-dendron 14 as the best candidate for bioconjugation; with subsequent bioconjugation producing a HER2-targeted therapeutic with average loading ratios of 15.4:1. In vitro evaluation of conjugate 18 demonstrated a nanomolar photocytotoxic effect in a target cell line, which overexpresses HER2, with no observed photocytotoxicity at the same concentration in a control cell line which expresses native HER2 levels, or in the absence of irradiation with visible light.
| Type: | Article |
|---|---|
| Title: | Assembly of high-potency photosensitiser-antibody conjugates through application of dendron multiplier technology |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.bioconjchem.7b00678 |
| Publisher version: | http://doi.org/10.1021/acs.bioconjchem.7b00678 |
| Language: | English |
| Additional information: | © 2017 American Chemical Society. This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10040408 |
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