Izvestiya of Saratov University.


ISSN 1817-3020 (Print)
ISSN 2542-193X (Online)

For citation:

Mordovina E. A., Berdenkova V. A., Bakal A. A., Tsyupka D. V., Kokorina A. A., Podkolodnaya Y. A., Goryacheva O. A., Goryacheva I. Y. Fluorescent nanosized PAMAM dendrimers: One-step formation of a bright blue fluorophore on terminal groups and its optical properties. Izvestiya of Saratov University. Physics , 2023, vol. 23, iss. 2, pp. 150-156. DOI: 10.18500/1817-3020-2023-23-2-150-156, EDN: MVEHVR

This is an open access article distributed under the terms of Creative Commons Attribution 4.0 International License (CC-BY 4.0).
Published online: 
Full text:
(downloads: 147)
Article type: 

Fluorescent nanosized PAMAM dendrimers: One-step formation of a bright blue fluorophore on terminal groups and its optical properties

Mordovina Ekaterina Alekseevna, Saratov State University
Berdenkova Victoria Alexandrovna, Saratov State University
Bakal Artem Alekseev, Saratov State University
Tsyupka Daria Vladislavovna, Saratov State University
Kokorina Alina A., Saratov State University
Podkolodnaya Yuliya A., Saratov State University
Goryacheva Olga A., Saratov State University
Goryacheva Irina Yurievna, Saratov State University

Background and Objectives: Polyamidoamine dendrimers (PAMAM) are nanoscale monodisperse compounds with a multifunctional terminal surface. Structural features of PAMAM, such as a nanosize of high homogeneity, highly developed terminal surface and cavities in the structure open up wide possibilities for their application. The most promising use of PAMAM is for biomedical purposes, in particular for the targeted drug delivery (for example, anticancer drugs). The interaction of PAMAM with target cells can be assessed using fluorescent imaging. This suggests the preliminary modification of PAMAM with various fluorescent molecules or the development of approaches to increase the intrinsic fluorescence of PAMAM. Materials and Methods: In this paper, we will consider a one-step modification of PAMAM based on the double cyclization reaction of PAMAM terminal groups and citric acid. Two approaches are chosen for modification: hydrothermal and boiling methods. The methods of optical spectroscopy and dynamic light scattering will be used as the main research tools. The methods used make it possible to determine the efficiency of fluorophore formation under given conditions. Results: In this work, we have proposed and implemented a one-step modification of PAMAM with a bright blue fluorophore (1,2,3,5-tetrahydro-5-oxo-imidazo[1,2-a] pyridine-7-carboxylic acid, IPCA), which is formed by a double cyclization reaction between citric acid and terminal ethylenediamine fragments of PAMAM. It has been shown that as a result of modification the hydrodynamic diameter of PAMAM does not change, the fluorescence intensity increases significantly (the quantum yield increases from < 1 to 28%), ζ-potential changes from 42 ± 5 to −24 ± 4 mV. Conclusion: Reaction of PAMAM and citric acid leads to the appearance of bright-blue fluorescence, which is significantly higher than the intrinsic fluorescence of PAMAM. A combination of bright fluorescence and a multifunctional terminal surface make it possible to further use the obtained structures for biovisualization.

This work was supported by the Russian Science Foundation (project No. 21-73-10046). Dynamic light scattering measurements were performed using Zetasizer Ultra (Resource Sharing Center of Saratov State University).
  1. Araújo R. V., Santos S. S., Ferreira E. I., Giarolla J. New advances in general biomedical applications of PAMAM dendrimers. Molecules, 2018, vol. 23, no. 11, article no. 2849. https://doi.org/10.3390/molecules23112849
  2. Xu X., Li J., Han S., Tao C., Fang L., Sun Y., Zhu J., Liang Z., Li F. A novel doxorubicin loaded folic acid conjugated PAMAM modified with borneol, a nature dual-functional product of reducing PAMAM toxicity and boosting BBB penetration. European Journal of Pharmaceutical Sciences, 2016, vol. 88, pp. 178–190. https://doi.org/10.1016/j.ejps.2016.02.015
  3. Tomalia D. A., Reyna L. A., Svenson S. Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging. Biochem. Soc. Trans., 2007, vol. 35, pp. 61–67. https://doi.org/10.1042/BST0350061
  4. Parsian M., Mutlu P., Yalcin S., Tezcaner A., Gunduz U. Half generations magnetic PAMAM dendrimers as an effective system for targeted gemcitabine delivery. International Journal of Pharmaceutics, 2016, vol. 515, pp. 104–113. https://doi.org/10.1016/j.ijpharm.2016.10.015
  5. Santos S., Ferreira E., Giarolla J. Dendrimer prodrugs. Molecules, 2016, vol. 21, article no. 686. https://doi.org/10.3390/molecules21060686
  6. Srinageshwar B., Peruzzaro S., Andrews M., Johnson K., Hietpas A., Clark B., McGuire C., Petersen E., Kippe J., Stewart A., Lossia O., Al-Gharaibeh A., Antcliff A., Culver R., Swanson D., Dunbar G., Sharma A., Rossignol J. PAMAM dendrimers cross the blood–brain barrier when administered through the carotid artery in C57BL/6J mice. International Journal of Molecular Sciences, 2017, vol. 18, article no. 628. https://doi.org/10.3390/ijms18030628
  7. Wen S., Liu H., Cai H., Shen M., Shi X. Targeted and pH-responsive delivery of doxorubicin to cancer cells using multifunctional dendrimer-modified multiwalled carbon nanotubes. Advanced Healthcare Materials, 2013, vol. 2, no. 9, pp. 1267–1276. https://doi.org/10.1002/adhm.201200389
  8. Siafaka P. I., Üstündaр N., Karavas E., Bikiaris D. N. Surface modified multifunctional and stimuli responsive nanoparticles for drug targeting: Current status and uses. International Journal of Molecular Sciences, 2016, vol. 17, no. 9, article no. 1440. https://doi.org/10.3390/ijms17091440
  9. Fu F., Wu Y., Zhu J., Wen S., Shen M., Shi X. Multifunctional lactobionic acid-modified dendrimers for targeted drug delivery to liver cancer cells: investigating the role played by PEG spacer. ACS Applied Materials & Interfaces, 2014, vol. 6, no. 18, pp. 16416–16425. https://doi.org/10.1021/am504849x
  10. Tsyupka D. V., Mordovina E. A., Sindeeva O. A., Sapelkin A. V., Sukhorukov G. B., Goryacheva I. Y. High-fluorescent product of folic acid photodegradation: Optical properties and cell effect. J. Photochem. Photobiol. A, 2021, vol. 407, article no. 113045. https://doi.org/10.1016/j.jphotochem.2020.113045
  11. Venditto V. J., Regino C. A. S., Brechbiel M. W. PAMAM dendrimer based macromolecules as improved contrast agents. Molecular Pharmaceutics, 2005, vol. 2, no. 4, pp. 302–311. https://doi.org/10.1021/mp050019e
  12. Wang D., Imae T. Fluorescence emission from dendrimers and its pH dependence. Journal of the American Chemical Society, 2004, vol. 126, no. 41, article no. 13204–13205. https://doi.org/10.1021/ja0454992
  13. Golshan M., Gheitarani B., Salami-Kalajahi M., Hosseini M. S. Synthesis and characterization of fluorescence poly (amidoamine) dendrimer-based pigments. Scientific Reports, 2022, vol. 12, pp. 15180. https://doi.org/10.1038/s41598-022-19712-5
  14. Camacho C. S. Urgellés M., Tomás H., Lahoz F., Rodrigues J. New insights into the blue intrinsic fluorescence of oxidized PAMAM dendrimers considering their use as bionanomaterials. Journal of Materials Chemistry B, 2020, vol. 8, no. 45, pp. 10314–10326. https://doi.org/10.1039/D0TB01871F
  15. Liang C., Huang J. F., Luo H., Sun D., Baker G. A., Dai S. Hydrophobic Bronsted Acid-Base Ionic Liquids Based on PAMAM Dendrimers with High Proton Conductivity and Blue Photoluminescence. Journal of the American Chemical Society, 2005, vol. 127, no. 37. pp. 12784–12785. https://doi.org/10.1021/ja053965x
  16. Jasmine M. J., Kavitha M., Prasad E. Effect of solvent-controlled aggregation on the intrinsic emission properties of PAMAM dendrimers. Journal of Luminescence, 2009, vol. 129, no. 5, pp. 506–513. https://doi.org/10.1016/j.jlumin.2008.12.005
  17. Song Y., Zhu S., Zhang S., Fu Y., Wang L., Zhao X., Yang B. Investigation from chemical structure to photoluminescent mechanism: A type of carbon dots from the pyrolysis of citric acid and an amine. Journal of Materials Chemistry C, 2015, vol. 3, no. 23, pp. 5976–5984. https://doi.org/10.1039/C5TC00813A
  18. Kasprzyk W., Bednarz S., Żmudzki P., Galica M., Bogdaі D. Novel efficient fluorophores synthesized from citric acid. RSC Advances, 2015, vol. 5, no. 44, pp. 34795–34799. https://doi.org/10.1039/c5ra03226a
  19. Kokorina A. A., Bakal A. A., Shpuntova D. V., Kostritskiy A. Y., Beloglazova N. V., Saeger S. De, Sukhorukov G. B., Sapelkin A. V., Goryacheva I. Y. Gel electrophoresis separation and origins of light emission in fluorophores prepared from citric acid and ethylenediamine. Scientific Reports, 2019, vol. 9, no. 1, article no. 14665. https://doi.org/10.1038/s41598-019-50922-6
  20. Podkolodnaya Y. A., Kokorina A. A., Goryacheva I. Y. A Facile Approach to the Hydrothermal Synthesis of Silica Nanoparticle/Carbon Nanostructure Luminescent Composites. Materials, 2022, vol. 15, no. 23, article no. 8469. https://doi.org/10.3390/ma15238469
  21. Mukherjee S. P., Davoren M., Byrne H. J. In vitro mammalian cytotoxicological study of PAMAM dendrimers–towards quantitative structure activity relationships. Toxicology In Vitro, 2010, vol. 24, pp. 169–177. https://doi.org/10.1016/j.tiv.2009.09.014
  22. Dobrovolskaia M. A., Patri A. K., Simak J., Hall J. B., Semberova J. De Paoli Lacerda S. H., McNeil S. E. Nanoparticle size and surface charge determine effects of PAMAM dendrimers on human platelets in vitro. Molecular Pharmaceutics, 2012, vol. 9, no. 3, pp. 382–393. https://doi.org/10.1021/mp200463e
  23. Fox L. J., Richardson R. M., Briscoe W. H. PAMAM dendrimer-cell membrane interactions. Advances in Colloid and Interface Science, 2018, vol. 257, pp. 1–18. https://doi.org/10.1016/j.cis.2018.06.0050001-8686