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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-07-01
|
| Series: | Materials & Design |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S026412752500632X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849688423250526208 |
|---|---|
| author | Abdelmnim Radoua Mélanie Romain Elisa Chazeau Nadège Marthouret Fabien Picaud Guillaume Herlem Christine Goze Nadine Millot Olivier Micheau |
| author_facet | Abdelmnim Radoua Mélanie Romain Elisa Chazeau Nadège Marthouret Fabien Picaud Guillaume Herlem Christine Goze Nadine Millot Olivier Micheau |
| author_sort | Abdelmnim Radoua |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-105b83e09bf1461d8b6f734eb66e4973 |
| institution | DOAJ |
| issn | 0264-1275 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj-art-105b83e09bf1461d8b6f734eb66e49732025-08-20T03:22:00ZengElsevierMaterials & Design0264-12752025-07-0125511421210.1016/j.matdes.2025.114212Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulationAbdelmnim Radoua0Mélanie Romain1Elisa Chazeau2Nadège Marthouret3Fabien Picaud4Guillaume Herlem5Christine Goze6Nadine Millot7Olivier Micheau8Université Bourgogne Europe, Inserm, CTM, DesCarTes, 21078 Dijon, FranceUniversité Bourgogne Europe, CNRS, Laboratoire Interdisciplinaire Carnot de Bourgogne ICB UMR 6303, 21000 Dijon, FranceUniversité Bourgogne Europe, CNRS, ICMUB UMR 6302, 21000 Dijon, FranceUniversité Marie et Louis Pasteur, UFR-ST, Laboratoire SINERGIES (UR 4662), Besançon 25030, FranceUniversité Marie et Louis Pasteur, UFR-ST, Laboratoire SINERGIES (UR 4662), Besançon 25030, FranceUniversité Marie et Louis Pasteur, UFR-ST, Laboratoire SINERGIES (UR 4662), Besançon 25030, FranceUniversité Bourgogne Europe, CNRS, ICMUB UMR 6302, 21000 Dijon, FranceUniversité Bourgogne Europe, CNRS, Laboratoire Interdisciplinaire Carnot de Bourgogne ICB UMR 6303, 21000 Dijon, FranceUniversité Bourgogne Europe, Inserm, CTM, DesCarTes, 21078 Dijon, France; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S026412752500632XGold nanorodsPro-apoptotic receptor activatorsStrain promoted azide-alkyne cycloadditionNIR activationAnti-tumor therapy |
| spellingShingle | Abdelmnim Radoua Mélanie Romain Elisa Chazeau Nadège Marthouret Fabien Picaud Guillaume Herlem Christine Goze Nadine Millot Olivier Micheau Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation Materials & Design Gold nanorods Pro-apoptotic receptor activators Strain promoted azide-alkyne cycloaddition NIR activation Anti-tumor therapy |
| title | Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation |
| title_full | Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation |
| title_fullStr | Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation |
| title_full_unstemmed | Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation |
| title_short | Bioorthogonal click chemistry-mediated conjugation of an anti-DR4 antibody to gold nanorods enhances its pro-apoptotic activity under near infra-red-light stimulation |
| title_sort | bioorthogonal click chemistry mediated conjugation of an anti dr4 antibody to gold nanorods enhances its pro apoptotic activity under near infra red light stimulation |
| topic | Gold nanorods Pro-apoptotic receptor activators Strain promoted azide-alkyne cycloaddition NIR activation Anti-tumor therapy |
| url | http://www.sciencedirect.com/science/article/pii/S026412752500632X |
| work_keys_str_mv | AT abdelmnimradoua bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT melanieromain bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT elisachazeau bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT nadegemarthouret bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT fabienpicaud bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT guillaumeherlem bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT christinegoze bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT nadinemillot bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation AT oliviermicheau bioorthogonalclickchemistrymediatedconjugationofanantidr4antibodytogoldnanorodsenhancesitsproapoptoticactivityundernearinfraredlightstimulation |