Assembly of High-Potency Photosensitizer-Antibody Conjugates through Application of Dendron Multiplier Technology.
Bioconjug Chem
; 29(1): 176-181, 2018 01 17.
Article
en En
| MEDLINE
| ID: mdl-29216717
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 15.41. 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Porfirinas
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Inmunoglobulina G
/
Fármacos Fotosensibilizantes
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Inmunoconjugados
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Dendrímeros
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Trastuzumab
Límite:
Humans
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia