Multifunctionalized Carbon Dots as an Active Nanocarrier for Drug Delivery to the Glioblastoma Cell Line

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Nanoparticle-based nanocarriers represent a viable alternative to conventional direct administration in cancer cells. This advanced approach employs the use of nanotechnology to transport therapeutic agents directly to cancer cells, thereby reducing the risk of damage to healthy cells and enhancing the efficacy of treatment. By approving nanoparticle-based nanocarriers, the potential for targeted, effective treatment is greatly increased. The so-called carbon-based nanoparticles, or carbon dots, have been hydrothermally prepared and initiated by a polymerization process. We synthesized and characterized nanoparticles of 2-acrylamido-2-methylpropanesulfonic acid, which showed biocompatibility with glioblastoma cells, and further, we tested them as a carrier for the drug riluzole. The obtained nanoparticles have been extensively characterized by techniques to obtain the exact composition of their surface by using Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and nuclear magnetic resonance (NMR) spectroscopy, as well as cryo-transmission electron microscopy. We found that the surface of the synthesized nanoparticles (NPs) is covered mainly by sulfonated, carboxylic, and substituted amide groups. These functional groups make them suitable as carriers for drug delivery in cancer cells. Specifically, we have successfully utilized the NPs as a delivery system for the drug riluzole, which has shown efficacy in treating glioblastoma cancer cells. The effect of nanoparticles as carriers for the riluzole system on glioblastoma cells was studied using live-cell synchrotron-based FTIR microspectroscopy to monitor in situ biochemical changes. After applying nanoparticles as nanocarriers, we have observed changes in all biomacromolecules, including the nucleic acids and protein conformation. These findings provide a strong foundation for further exploration into the development of targeted treatments for glioblastoma.

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The authors are grateful for financial support from the Spanish Ministry of Science and Innovation (MCIN/AEI/10.13039/ 501100011033) through project PID2021-122613OB-I00 as well as the ALBA In-house grant: “Synergetic multimodal FTIR and X-ray spectro-microscopical approach for 3D cell culture evaluation”. Open access funding is provided by Universidad Publica ́ de Navarra. The authors are grateful to Professor Veit Rohde, Dr. Milena Ninkovic, and Swetlana Sperling, Department of Neurosurgery, University Medical Center Göttingen, Germany, for cell providing and support for the cell culturing. The authors thank Dr. Pablo Guerra from the IBMB-CSIC CryoEM Platform for assistance during the sample preparation and microscope data acquisition. The authors acknowledge funding from Project, IU16-014045 (CRYO-TEM) from Generalitat de Catalunya and by “ERDF A way of making Europe”, by the European Union. The authors are thankful to Dragoljub Dimitrijevic for assistance during the spectroscopical measurements. JS thanks R. Larrosa and D. Guerrero for the technical support in running the calculations and the SCBI (Supercomputer and Bioinformatics) center of the University of Málaga for computer resources.

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Multifunctionalized Carbon Dots as an Active Nanocarrier for Drug Delivery to the Glioblastoma Cell Line Manuel Algarra, Juan Soto, Maria Soledad Pino-González, Elena Gonzalez-Munoz, and Tanja Dučić ACS Omega 2024 9 (12), 13818-13830 DOI: 10.1021/acsomega.3c08459

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