Izvestiya of Saratov University.

Physics

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


For citation:

Lazareva E. N., Mylnikov A. M., Navolokin N. A., Doronkina A. A., Anisimov R. A., Lomova M. V., Kochubey V. I., Yanina I. Y. Influence of upconversion nanoparticles on the refractive properties of tumor tissue under photodynamic therapy. Izvestiya of Saratov University. Physics , 2025, vol. 25, iss. 3, pp. 343-355. DOI: 10.18500/1817-3020-2025-25-3-343-355, EDN: PGBLUU

This is an open access article distributed under the terms of Creative Commons Attribution 4.0 International License (CC-BY 4.0).
Published online: 
29.08.2025
Full text:
(downloads: 127)
Language: 
Russian
Article type: 
Article
UDC: 
616-073.53
EDN: 
PGBLUU

Influence of upconversion nanoparticles on the refractive properties of tumor tissue under photodynamic therapy

Autors: 
Lazareva Ekaterina Nikolaevna, Saratov State University
Mylnikov Artyom M., Saratov State Medical University named after V. I. Razumovsky
Navolokin Nikita A., Saratov State Medical University named after V. I. Razumovsky
Doronkina Anna A., Saratov State University
Anisimov Roman A., Saratov State University
Lomova Maria V., Saratov State University
Kochubey Vyacheslav Ivanovich, Saratov State University
Yanina Irina Yu., Saratov State University
Abstract: 

Background and Objectives: To develop and improve the efficiency of minimally invasive cancer therapy methods, accurate data on the optical properties of biological tissues and their changes after photodynamic therapy using upconversion nanoparticles (UCNPs) of various types are required. One of the optical methods proposed for diagnostics and assessment of tumor tissue development is the method of multiwave refractometry. Materials and methods: In the presented study, a model of alveolar liver cancer (cholangiocarcinoma, PC1) development in rats was used. Photodynamic therapy was carried out using 5 different UCNPs. The refractive index was measured on an Abbe DR-M2/1550 multiwave refractometer (Atago, Japan). Results: The dispersion dependence of tissue samples of model alveolar liver cancer was analyzed in the spectral range of 480–1550 nm after the introduction of 5 different types of UCNPs, as well as after photodynamic therapy. According to the obtained result, the highest value of the Abbe number (53.67 ± 0.68) is characteristic of intact tumor tissue, while UCNPs lead to a decrease in the Abbe number (53.29 ± 0.69), an even lower value of the Abbe number (53.12 ± 0.69) is observed in tissue samples from groups of animals after photodynamic therapy. Conclusions: The results presented in this paper have shown that the introduction of UCNPs of various types and the use of photodynamic therapy cause a change in the refractometric properties of tissues. The presented results can be useful for many methods of laser therapy and optical diagnostics of skin diseases and localization of subcutaneous tumors.

Acknowledgments: 
The work was supported by the Russian Science Foundation (project No. 21–72–10057, https://rscf.ru/project/21-72-10057/).
Reference: 
  1. Hu T., Wang Z., Shen W., Liang R., Yan D., Wei M. Recent advances in innovative strategies for enhanced cancer photodynamic therapy. Theranostics, 2021, vol. 11, no. 7, pp. 3278–3300. https://doi.org/10.7150/thno.54227
  2. Chang H., Xie J., Zhao B., Liu B., Xu S., Ren N., Xie X., Huang L., Huang W. Rare earth ion-doped upconversion nanocrystals: Synthesis and surface modification. Nanomaterials, 2015, vol. 5, no. 1, pp. 1–25. https://doi.org/10.3390/nano5010001
  3. Abdel-Kader M. H. Photodynamic Therapy. Berlin, Springer, 2016. 317 p. https://doi.org/10.1007/978-3-642-39629-8
  4. Filonenko E. V. Fluorescence diagnostics and photodynamic therapy: Justification of applications and opportunities in oncology. Photodynamic Therapy and Photodiagnosis, 2014, no. 1, pp. 3–7 (in Russian).
  5. Yanina I. Yu., Kochubey V. I. Toxicity of upconversion nanoparticles. Overview. Izvestiya of Saratov Univercity. Physics, 2020, vol. 20, iss. 4, pp. 268–277 (in Russian). https://doi.org/10.18500/1817-3020-2020-20-4-268-277
  6. Doronkina A. A., Kochubey V. I., Maksutova A. V., Pravdin A. B., Mylnikov A. M., Navolokin N. A., Yanina I. Y. NaYF4: Yb, Er Upconversion nanoparticles for imaging: effect on red blood cells. Photonics, 2023, vol. 10, no. 12, art. 1386. https://doi.org/10.3390/photonics10121386
  7. DeRosa M. C., Crutchley R. J. Photosensitized singlet oxygen and its applications. Coordination Chemistry Reviews, 2002, vol. 233–234, pp. 351–371. https://doi.org/10.1016/S0010-8545(02)00034-6
  8. Stella B., Arpicco S., Peracchia M. T., Desmaële D., Hoebeke J., Renoir M., D’Angelo J., Cattel L., Couvreur P. Design of folic acid-conjugated nanoparticles for drug targeting. Journal of Pharmaceutical Sciences, 2000, vol. 89, no. 1, pp. 1452–1464. https://doi.org/10.1002/1520- 6017(200011)89:11\char”003C\relax1452::aid-jps8\char”003E\relax3.0.co;2-p
  9. Kochubey V. I., Yanina I.Yu. Application of upconversion nanoparticles as a temperature sensor for biological tissue. Photon Express, 2023, no. 6 (190), pp. 354–355 (in Russian). https://doi.org/10.24412/2308-6920-2023-6-354-355
  10. Carneiro I., Carvalho S., Henrique R., Oliveira L., Tuchin V. V. Measurement of optical properties of normal and pathological human liver tissue from deepUV to NIR. Proc. SPIE, 2020, vol. 11363, art. 113630G. https://doi.org/10.1117/12.2554877
  11. Nazarov M. M., Cherkasova O. P., Lazareva E. N., Bucharskaya A. B., Navolokin N. A., Tuchin V. V., Shkurinov A. P. A complex study of the peculiarities of blood serum absorption of rats with experimental liver cancer. Optics and Spectroscopy, 2019, vol. 126, no. 6, pp. 721–729. https://doi.org/10.1134/S0030400X19060183
  12. Gul B., Ashraf S., Khan S., Nisar H., Ahmad I. Cell refractive index: Models, insights, applications and future perspectives. Photodiagnosis Photodyn. Ther., 2021, vol. 33, art. 102096. https://doi.org/10.1016/j.pdpdt.2020.102096
  13. Ledwig P., Robles F. E. Quantitative 3D refractive index tomography of opaque samples in epi-mode. Optica, 2021, vol. 8, iss. 1, pp. 6–14. https://doi.org/10.1364/OPTICA.410135
  14. Wang J., Deng Z., Zhou W., Zhang C., Tian J. Measurement of the complex refractive index of tissue-mimicking phantoms and biotissue by extended differential total reflection method. J. Biomed. Opt., 2011, vol. 16, no. 9, art. 097001. https://doi.org/10.1117/1.3615657
  15. Martins I. S., Silva H. F., Lazareva E. N., Chernomyrdin N. V., Zaytsev K. I., Oliveira L. M., Tuchin V. V. Measurement of tissue optical properties in a wide spectral range: A review [Invited]. Biomed Opt Express, 2022, vol. 14, iss. 1, pp. 249–298. https://doi.org/10.1364/BOE.479320
  16. Contreras-Tello H., Márquez-Islas R., Vázquez-Estrada O., Sánchez-Pérez C., García-Valenzuela A. Understanding the performance of Abbe-type refractometers with optically absorbing fluids. Meas. Sci. Technol., 2014, vol. 25, art. 075201. https://doi.org/10.1088/0957-0233/25/7/075201
  17. Wang Z., Tangella K., Balla A., Popescu G. Tissue refractive index as marker of disease. J. Biomed. Opt., 2011, vol. 16, no. 11, art.116017. https://doi.org/10.1117/1.3656732
  18. Giannios P., Koutsoumpos S., Toutouzas K. G., Matiatou M., Zografos G. C., Moutzouris K. Complex refractive index of normal and malignant human colorectal tissue in the visible and near-infrared. J. Biophotonics, 2017, vol. 10, no. 2, pp. 303–310. https://doi.org/10.1002/jbio.201600001
  19. Tarahovskij Yu. S. Intellektualnye lipidnye nanokontejnery v adresnoj dostavke lekarstvennyh veshchestv [Intelligent Lipid Nanocontainers in Targeted Drug Delivery]. Moscow, Editorial URS, 2011. 280 p. (in Russian).
  20. Torresan M. F., Wolosiuk Al. Critical aspects on the chemical stability of NaYF4 – Based upconverting nanoparticles for biomedical applications. ACS Applied Bio Materials., 2021, vol. 4, iss. 2, pp. 1191–1210. https://doi.org/10.1021/acsabm.0c01562
  21. Alnasif N., Zoschke C., Fleige E., Brodwolf R., Boreham A., Rühl E., Eckl K. M., Merk H. F., Hennies H. C., Alexiev U., Haag R., Küchler S., Schäfer-Korting M. Penetration of normal, damaged and diseased skin – An in vitro study on dendritic core-multishell nanotransporters. Journal of Controlled Release, 2014, vol. 185, pp. 45–50. https://doi.org/10.1016/j.jconrel.2014.04.006
  22. Carneiro I., Carvalho S., Henrique R., Oliveira L., Tuchin V. V. Measuring optical properties of human liver between 400 and 1000 nm. Quant. Elect., 2019, vol. 49, no.1, pp. 13–19. https://doi.org/10.1070/QEL16903
  23. Bucharskaya A. B., Dikht N. I., Afanas’eva G. A., Terentyuk G. S., Zakharova N. B., Maslyakova G. N., Khlebtsov B. N., Khlebtsov N. G. The assessment of molecular markers of cell interaction and lipid peroxidation in rats with alloxan diabetes and trans- planted liver cancer after intravenous injection of gold nanorods // Saratov Journal of Medical Scientific Research, 2015, vol. 11, no. 2, pp. 107–112 (in Russian).
  24. International Guiding Principles for Biomedical Research Involving Animals. CIOMS and ICLAS. 2012. Available at: https://olaw.nih.gov/sites/default/files/Guiding_Principles_2012.pdf (accessed April 10, 2024).
  25. Lazareva E. N., Oliveira L., Yanina I. Yu., Chernomyrdin N. V., Musina G. R., Tuchina D. K., Bashkatov A. N., Zaytsev K. I., Tuchin V. V. Refractive index measurements of tissue and blood components and OCAs in a wide spectral range. In: Tuchin V. V., Zhu D., Genina E. A. Handbook of Tissue Optical Clearing: New Prospects in Optical Imaging, 2022, pp. 141–166. https://doi.org/10.1201/9781003025252
  26. Kasap S. O., Capper P. Springer handbook of electronic and photonic materials. Cham, Springer, 2006. 1406 p. https://doi.org/10.1007/978-3-319-48933-9
  27. Zysk A., Adie S., Armstrong J., Leigh M., Paduch A., Sampson D. Needle-based refractive index measurement using low-coherence interferometry. Opt. Express, 2007, vol. 32, no. 4, pp. 385–387. https://doi.org/10.1364/OL.32.000385
  28. Daimon M., Masumura A. Measurement of the refractive index of distilled water from the near-infrared region to the ultraviolet region. Appl. Opt., 2007, vol. 46, pp. 3811–3820. https://doi.org/10.1364/AO.46.003811
  29. Bashkatov A. N., Genina E. A. Water refractive index in dependence on temperature and wavelength: a simple approximation. Proc. SPIE, 2003, vol. 5060, pp. 393–395. https://doi.org/10.1117/12.518857
  30. Thormählen I., Straub J., Grigull U. Refractive Index of Water and its Dependence on Wavelength, Temperature, and Density. J. Phys. Chem. Ref. Data, 1985, vol. 14, no. 4, pp. 933–945. https://doi.org/10.1063/1.555743
  31. Harvey A. H., Gallagher J. S., Sengers J. M. H. L. Revised formulation for the refractive index of water and steam as a function of wavelength, Temperature and Density. J. Phys. Chem. Ref. Data, 1998, vol. 27, iss. 4, pp. 761–774. https://doi.org/10.1063/1.556029
  32. Bertie J. E., Lan Z. Infrared Intensities of Liquids XX: The intensity of the OH stretching band of liquid water revisited, and the best current values of the optical constants of H2O at 25°C between 15,000 and 1 cm−1. Appl. Spectrosc., 1996, vol. 50, no. 8, pp. 1047–1057. https://doi.org/10.1366/0003702963905385
  33. Hale G. M., Querry M. R. Optical constants of water in the 200-nm to 200-Mm wavelength region. Appl. Opt., 1973, vol. 12, iss. 3, pp. 555–562. https://doi.org/10.1364/AO.12.000555
  34. Kedenburg S., Vieweg M., Gissibl T., Giessen H. Linear Refractive index and absorption measurements of nonlinear optical liquids in the visible and Near-Infrared spectral region, Opt. Mater. Express, 2012, vol. 2, no. 1, pp. 1588–1611. https://doi.org/10.1364/OME.2.001588
  35. Lue N., Kang J. W., Hillman T. R., Dasari R. R., Yaqoob Z. Single-shot quantitative dispersion phase microscopy. Appl. Phys. Lett., 2012, vol. 101, iss. 8, art. 084101. https://doi.org/10.1063/1.4745785
Received: 
22.04.2024
Accepted: 
10.07.2025
Published: 
29.08.2025