Assembly of High-Potency Photosensitizer–Antibody Conjugates through Application of Dendron Multiplier Technology
| Autor: | Miffy. H. Y. Cheng, Vijay Chudasama, Francesca Bryden, João M. M. Rodrigues, Huguette Savoie, Ross W. Boyle, Andrew Beeby, Antoine Maruani |
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| Rok vydání: | 2017 |
| Předmět: |
Dendrimers
Immunoconjugates Porphyrins Cell Survival Receptor ErbB-2 Biomedical Engineering Pharmaceutical Science Bioengineering 010402 general chemistry 01 natural sciences Absorbance chemistry.chemical_compound Drug Delivery Systems Cell Line Tumor Neoplasms Dendrimer Humans Photosensitizer Cytotoxicity Pharmacology Photosensitizing Agents Bioconjugation 010405 organic chemistry Chemistry Singlet oxygen Organic Chemistry Trastuzumab Combinatorial chemistry In vitro 0104 chemical sciences Immunoglobulin G Biotechnology Conjugate |
| Zdroj: | Bioconjugate chemistry, 2018, Vol.29(1), pp.176-181 [Peer Reviewed Journal] |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/acs.bioconjchem.7b00678 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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