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Assembly of high-potency photosensitizer-antibody conjugates through application of dendron multiplier technology

Rodrigues, João M.M.; Cheng, Miffy H.Y.; Bryden, Francesca; Maruani, Antoine; Rodrigues, João M. M.; Cheng, Miffy H. Y.; Savoie, Huguette; Beeby, Andrew; Chudasama, Vijay; Boyle, Ross W.

Authors

João M.M. Rodrigues

Miffy H.Y. Cheng

Francesca Bryden

Antoine Maruani

João M. M. Rodrigues

Miffy H. Y. Cheng

Huguette Savoie

Andrew Beeby

Vijay Chudasama



Abstract

© 2017 American Chemical Society. Exploitation of photosensitizers as payloads for antibody-based anticancer therapeutics offers a novel alternative to the small pool of commonly utilized 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.

Journal Article Type Article
Publication Date Jan 17, 2018
Journal Bioconjugate chemistry
Print ISSN 1043-1802
Electronic ISSN 1520-4812
Publisher American Chemical Society
Peer Reviewed Peer Reviewed
Volume 29
Issue 1
Pages 176-181
APA6 Citation Rodrigues, J. M., Cheng, M. H., Bryden, F., Maruani, A., Rodrigues, J. M. M., Cheng, M. H. Y., …Boyle, R. W. (2018). Assembly of high-potency photosensitizer-antibody conjugates through application of dendron multiplier technology. Bioconjugate chemistry, 29(1), 176-181. https://doi.org/10.1021/acs.bioconjchem.7b00678
DOI https://doi.org/10.1021/acs.bioconjchem.7b00678
Keywords Biotechnology; Organic Chemistry; Bioengineering; Pharmacology; Pharmaceutical Science; Biomedical Engineering
Publisher URL http://pubs.acs.org/doi/10.1021/acs.bioconjchem.7b00678
Copyright Statement ©2018 University of Hull
Additional Information This document is the Accepted Manuscript version of a Published Work that appeared in final form in Bioconjugate Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.bioconjchem.7b00678

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