Assembly of High-Potency Photosensitizer-Antibody Conjugates through Application of Dendron Multiplier Technology
authors Bryden, F; Maruani, A; Rodrigues, JMM; Cheng, MHY; Savoie, H; Beeby, A; Chudasama, V; Boyle, RW
nationality International
journal BIOCONJUGATE CHEMISTRY
keywords PHOTODYNAMIC THERAPY; CLICK CHEMISTRY; NEXT-GENERATION; STABILITY; MILD; PHTHALOCYANINE; PORPHYRINS; STRATEGIES; ADCS
abstract 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.
publisher AMER CHEMICAL SOC
issn 1043-1802
year published 2018
volume 29
issue 1
beginning page 176
ending page 181
digital object identifier (doi) 10.1021/acs.bioconjchem.7b00678
web of science category Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic
subject category Biochemistry & Molecular Biology; Chemistry
unique article identifier WOS:000423012800021
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journal impact factor 4.031
5 year journal impact factor 4.267
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