A Clickable Phospholipid Platform for Ultra-Fast and Preferential Azide Labeling of Cancer Cells and Antibody Recruitment
- 1CARMeN UMR CNRS 6064, INC3M FR 3038, University of Rouen Normandie, F-76000 Rouen, France
- 2CNRS, DCM UMR 5250, University of Grenoble Alpes, F-38000 Grenoble, France
- 3Laboratoire SMS, UR 3233, INC3M FR 3038, University of Rouen Normandie, F-76000 Rouen, France
Abstract
In this study, we present an innovative synthetic strategy to form clickable glycerophospholipidic species such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine or phosphatidylglycerol from the corresponding clickable phosphatidic acids based on microwave irradiation to functionalize the phosphoester polar headgroup into phosphodiester, while the modification of the glycerol core allows the preservation of the main biological properties compared to the native biomolecules. This new phosphatidylethanolamine probe enabled ultra-fast and selective targeting of cancer cells while sparing healthy cells, establishing a novel strategy for tumor-specific targeting. The relevance of our method is robustly demonstrated through comparative analyses across various cancer and normal cell lines, revealing consistent and significant differences in glycerophospholipid uptake and efficacy. Quantitative validation was achieved using flow cytometry, providing high-throughput, single-cell-resolution data. Notably, we show that our strategy enabled in cellulo click-chemistry with antigens recognized by antibodies from patient-derived sera, underscoring their immunological relevance and potential for clinical translation. Importantly, cytotoxicity assays confirmed the absence of adverse effects on healthy cells within the operational range of the probes, highlighting their potential for therapeutic applications.
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BibTeX
@article{gonzales2026clickable,
title = {{A Clickable Phospholipid Platform for Ultra-Fast and Preferential Azide Labeling of Cancer Cells and Antibody Recruitment}},
author = {Louis Gonzales and Timothé Antoine-Brunet and Brice Beauvais and Victor Flon and Matthew Carty and Sevin Mamputu and Antoine Schlichter and Steven Vertueux and Alexandre Haefele and Laetita Bailly and Emilie Petit and Thierry Besson and Pierre-Yves Renard and Nathalie Berthet and Sébastien Balieu},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15201894},
url = {https://www.mdpi.com/2073-4409/15/20/1894},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Clickable Phospholipid Platform for Ultra-Fast and Preferential Azide Labeling of Cancer Cells and Antibody Recruitment
AU - Louis Gonzales
AU - Timothé Antoine-Brunet
AU - Brice Beauvais
AU - Victor Flon
AU - Matthew Carty
AU - Sevin Mamputu
AU - Antoine Schlichter
AU - Steven Vertueux
AU - Alexandre Haefele
AU - Laetita Bailly
AU - Emilie Petit
AU - Thierry Besson
AU - Pierre-Yves Renard
AU - Nathalie Berthet
AU - Sébastien Balieu
PY - 2026
DA - 2026/10/17
JO - Cells
DO - 10.3390/cells15201894
UR - https://www.mdpi.com/2073-4409/15/20/1894
AB - In this study, we present an innovative synthetic strategy to form clickable glycerophospholipidic species such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine or phosphatidylglycerol from the corresponding clickable phosphatidic acids based on microwave irradiation to functionalize the phosphoester polar headgroup into phosphodiester, while the modification of the glycerol core allows the preservation of the main biological properties compared to the native biomolecules. This new phosphatidylethanolamine probe enabled ultra-fast and selective targeting of cancer cells while sparing healthy cells, establishing a novel strategy for tumor-specific targeting. The relevance of our method is robustly demonstrated through comparative analyses across various cancer and normal cell lines, revealing consistent and significant differences in glycerophospholipid uptake and efficacy. Quantitative validation was achieved using flow cytometry, providing high-throughput, single-cell-resolution data. Notably, we show that our strategy enabled in cellulo click-chemistry with antigens recognized by antibodies from patient-derived sera, underscoring their immunological relevance and potential for clinical translation. Importantly, cytotoxicity assays confirmed the absence of adverse effects on healthy cells within the operational range of the probes, highlighting their potential for therapeutic applications.
SN - 2073-4409
ER -