Nanoparticles improve targeting and efficacy of endocytosis inhibitors.
8 affiliations
- 1Department of Synthesis and Technology of Drugs, Medical University of Bialystok Kilinskiego 1 15-089 Bialystok Poland [email protected].
- 2Department of Biotechnology, Medical University of Białystok Kilinskiego 1 15-089 Bialystok Poland.
- 3Faculty of Chemistry, University of Bialystok Ciolkowskiego 1K Bialystok Poland.
- 4Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University Pekarska 69 79010 Lviv Ukraine.
- 5Molecular Design Center, Danylo Halytsky Lviv National Medical University Pekarska 69 79010 Lviv Ukraine.
- 6Department of Pharmaceutical Chemistry, National Pirogov Memorial Medical University Pirogova 56 21018 Vinnytsya Ukraine.
- 7Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow Sucharskiego 2 35-225 Rzeszow Poland.
- 8CNRS UMR9018 Institut Gustave Roussy, Université Paris Saclay 39 Rue Camille-Desmoulins 94805 Villejuif France.
Abstract
Endocytosis is a critical cellular process exploited by many viruses, including HIV-1 and SARS-CoV-2, for host cell entry. Inhibiting this pathway provides a promising antiviral strategy; however, existing small-molecule inhibitors often suffer from limited solubility, off-target effects, and poor bioavailability. This study reports the synthesis and evaluation of gold nanoparticles functionalized with novel endocytosis inhibitors, Les-6623 and Les-6632. The compounds were synthesized via a linear Knoevenagel condensation pathway and structurally confirmed by NMR and LC-MS spectroscopy. Molecular docking predicted more favorable interactions of Les-6623 and Les-6632 with dynamin-2 than those predicted for chlorpromazine, a classical endocytosis inhibitor. PEGylated gold nanoparticles were functionalized with the inhibitors, yielding formulations characterized by UV-Vis, fluorescence spectroscopy, ATR-FTIR, DLS, and TEM analyses. Functional assays in SH-SY5Y and BEAS-2B cells showed that AuNP_Les-6623 and AuNP_Les-6632 reduced the cellular fluorescence associated with transferrin, HIV-1 Tat, and SARS-CoV-2 Spike protein under the experimental conditions tested. Free chlorpromazine was included as a reference inhibitor. These findings support the biological activity of the investigated nanoparticle formulations under the tested conditions, while further format-matched controls are required to determine the specific contribution of nanoparticle presentation to the observed activity.
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BibTeX
@article{szewczykroszczenko2026nanoparticles,
title = {{Nanoparticles improve targeting and efficacy of endocytosis inhibitors.}},
author = {Olga Klaudia Szewczyk-Roszczenko and Piotr Roszczenko and Iwona Misztalewska-Turkowicz and Rostyslav Dudchak and Ihor Yushyn and Yulia Shepeta and Serhii Holota and Anna Bielawska and Robert Czarnomysy and Roman Lesyk and Agnieszka Wilczewska and Yegor Vassetzky and Krzysztof Bielawski},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra07148a},
url = {https://europepmc.org/article/MED/42923754},
note = {CC BY},
}
RIS
TY - JOUR
TI - Nanoparticles improve targeting and efficacy of endocytosis inhibitors.
AU - Olga Klaudia Szewczyk-Roszczenko
AU - Piotr Roszczenko
AU - Iwona Misztalewska-Turkowicz
AU - Rostyslav Dudchak
AU - Ihor Yushyn
AU - Yulia Shepeta
AU - Serhii Holota
AU - Anna Bielawska
AU - Robert Czarnomysy
AU - Roman Lesyk
AU - Agnieszka Wilczewska
AU - Yegor Vassetzky
AU - Krzysztof Bielawski
PY - 2026
DA - 2026/10/22
JO - RSC advances
DO - 10.1039/d6ra07148a
UR - https://europepmc.org/article/MED/42923754
AB - Endocytosis is a critical cellular process exploited by many viruses, including HIV-1 and SARS-CoV-2, for host cell entry. Inhibiting this pathway provides a promising antiviral strategy; however, existing small-molecule inhibitors often suffer from limited solubility, off-target effects, and poor bioavailability. This study reports the synthesis and evaluation of gold nanoparticles functionalized with novel endocytosis inhibitors, Les-6623 and Les-6632. The compounds were synthesized via a linear Knoevenagel condensation pathway and structurally confirmed by NMR and LC-MS spectroscopy. Molecular docking predicted more favorable interactions of Les-6623 and Les-6632 with dynamin-2 than those predicted for chlorpromazine, a classical endocytosis inhibitor. PEGylated gold nanoparticles were functionalized with the inhibitors, yielding formulations characterized by UV-Vis, fluorescence spectroscopy, ATR-FTIR, DLS, and TEM analyses. Functional assays in SH-SY5Y and BEAS-2B cells showed that AuNP_Les-6623 and AuNP_Les-6632 reduced the cellular fluorescence associated with transferrin, HIV-1 Tat, and SARS-CoV-2 Spike protein under the experimental conditions tested. Free chlorpromazine was included as a reference inhibitor. These findings support the biological activity of the investigated nanoparticle formulations under the tested conditions, while further format-matched controls are required to determine the specific contribution of nanoparticle presentation to the observed activity.
SN - 2046-2069
ER -