Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation

Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation

Pro-apoptotic receptor activators (PARAs), including second-generation agonist antibodies and ligands targeting the TNF receptor superfamily such as TRAIL (TNF-Related Apoptosis-Inducing Ligand), represent a promising class of cancer therapeutics. Enhancing their apoptotic efficacy through multivale...

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Bibliographic Details
Main Authors: Abdelmnim Radoua, Mélanie Romain, Elisa Chazeau, Nadège Marthouret, Fabien Picaud, Guillaume Herlem, Christine Goze, Nadine Millot, Olivier Micheau
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Materials & Design
Subjects:
Gold nanorods
Pro-apoptotic receptor activators
Strain promoted azide-alkyne cycloaddition
NIR activation
Anti-tumor therapy
Online Access:http://www.sciencedirect.com/science/article/pii/S026412752500632X
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Summary:Pro-apoptotic receptor activators (PARAs), including second-generation agonist antibodies and ligands targeting the TNF receptor superfamily such as TRAIL (TNF-Related Apoptosis-Inducing Ligand), represent a promising class of cancer therapeutics. Enhancing their apoptotic efficacy through multivalency or controlled thermal stimulation has been previously demonstrated. In this study, we report the design and optimization of gold nanorod (GNR)-based nanoconjugates for targeted PARA delivery under near-infrared (NIR)-induced mild hyperthermia. Three conjugation strategies—EDC/NHS coupling, Schiff base formation, and strain-promoted azide–alkyne cycloaddition (SPAAC)—were systematically evaluated. Surface functionalization of GNRs with –COOH, –NH2, and −DBCO groups was confirmed via UV–vis spectroscopy, surface-enhanced Raman spectroscopy (SERS), X-ray photoelectron spectroscopy (XPS), zeta potential analysis, and transmission electron microscopy (TEM). Bioactivity assays indicated that SPAAC-mediated click chemistry enabled superior retention of PARA functionality compared to conventional methods. Notably, GNRs conjugated with an anti-DR4 antibody selectively triggered apoptosis in cancer cells upon NIR exposure. These results demonstrate that SPAAC-mediated functionalization enables precise, bioactive nanocarriers for enhanced cancer cell apoptosis under photothermal control.
ISSN:0264-1275

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