CC BY
4DOI 10.24412/CL-37135-2023-1-25-26
EFFECT OF THE DOSE OF UPCONVERSION NANOPARTICLES ON THE REFRACTIVE INDEX OF TISSUES IN THE DEVELOPMENT OF MODEL LIVER
CANCER
EKATERINA LAZAREVA1,2, ROMAN ANISIMOV1, MARIA LOMOVA1, ANNA DORONKINA1, ARTEM MYLNIKOV3, NIKITA NAVOLOKIN3, VYACHESLAV KOCHUBEY1
AND IRINA YANINA1,2
Scientific and Educational Institute of Optics and Biophotonics, Saratov State University, Russia Interdisciplinary Laboratory of Biophotonics, National Research Tomsk State University, Russia 3 Department of Pathological Anatomy, Saratov State Medical University, Russia
ABSTRACT
Upconversion nanoparticles(UCNP) play an important role in the application of photodynamic therapy, which helps to treat malignant tumors with high efficiency [1, 2]. Since the development of pathology changes the structure and composition of biological tissues, and, consequently, their optical properties undergo significant changes, several research groups have proposed using the refractive index, as one of the main optical parameters, as a marker for differentiating normal and pathological biological tissue , including experimental diabetes in animals [3]. Also, the refractive index is an important optical characteristic that is necessary for a complete description of the optical properties of biological tissues.
The presented study was carried out on white mature Wistar rats, according to the method described in the article [4]. When conducting experiments on animals, accepted international ethical standards were observed [5]. The study modeled the development of alveolar liver cancer (cholangiocarcinoma, PC1) by injecting 0.5 ml of a 25% tumor suspension in Hanks solution subcutaneously into the scapula area. Animals were removed from the experiment on day 28 after tumor implantation. Laboratory animals with transplanted liver tumors were injected with various doses (one, two and three times) of solutions of UCNP NaYF4 with a solution of bovine serum albumin (BSA) and folic acid (FA) (concentration 2 mg/ml).
The refractive index was measured on a multi-wavelength Abbe refractometer DR-M2/1550 (Atago, Japan) using 12 interference filters for the spectral region 480-1550 nm. To isolate wavelengths, narrow-band interference filters were used for 480, 486, 546, 589, 644, 656, 680, 800, 930, 1100, 1300, 1550 nm.
Data for refractive indices at a wavelength of 589 nm for tissues after the introduction of single, double and triple doses of NaYF4+BSA+FA nanoparticles are presented in Table 1.
Table 1. Refractive index at 589 nm for tissues after administration of various doses of UCNP
_Skin_
Single dose_1.3557
Double dose_1.3723
Triple dose_1.3753
Subcutaneous adipose tissue
Single dose_1.3797
Double dose_1.3946
Triple dose_1.3937
_Muscle tissue_
Single dose_1.3449
Double dose_1.3598
Triple dose_1.3697
Tumor tissue (model liver cancer)
Single dose_1.3459
Double dose_1.3623
Triple dose_1.4018
Figure 1 shows the dispersion dependences for various tissues taken in the area of tumor development after the introduction of NaYF4 + BSA + FA UCNP in single, double and triple doses.
600 800 1000 1200 1400 1600 Wavelength, nm
A
600 800 1000 1200 1400 1600 Wavelength, nm
C
Adipose tissue, NaYF4+BSA+FA, 1 dose Adipose tissue, NaYF4+BSA+FA, 2 dose Adipose tissue, NaYF4+BSA+FA, 3 dose
~800-1000—1200—1400—1600"
Wavelength, nm
B
600 800 1000 1200 1400 1600 Wavelength, nm
D
400 600
Figure 1: Dispersion dependence of altered biological tissues after the introduction of various doses of nanoparticles:
A - skin samples after administration of NaYF4+BSA+FA;
B - samples of subcutaneous adipose tissue after administration of NaYF4+BSA+FA;
C - muscle tissue samples after administration of NaYF4+BSA+FA;
D - samples of model liver cancer after administration of NaYF4+BSA+FA
According to the data obtained, for all tissues there is an increase in the refractive index with an increase in the administered dose of nanoparticles. The refractive index at a wavelength of 589 nm for tumor tissue was equal to 1.3459 for a single, 1.3623 for a double and 1.4018 for a triple dose of NaYF4 + BSA + FA. An increased value of the refractive index may indicate the accumulation of nanoparticles in the tumor tissue and other tissues located in the area tumor development.
Thus, the injection of nanoparticles in different doses causes changes in the refractometric properties of tissues. Analysis of the refractive indices of various biological tissues after the introduction of various doses of nanoparticles of this type showed that tissues with a higher dose administered are characterized by a higher refractive index than tissue samples taken near the site of tumor development with the introduction of nanoparticles of lower doses. The result may be related to the accumulation of nanoparticles in tumor tissue and surrounding tissues and suggests that refractive index can be used to assess the accumulation of nanoparticles in tissues.
The study was supported by RSF grant no. 21-72-10057, https://rscf.ru/proiect721 -72-10057/.
REFERENCES
[1] M.H. Abdel-Kader, Photodynamic therapy. - Berlin: Springer-Verlag, p. 317. 2016.
[2] E.V. Filonenko, Fluorescence diagnostics and photodynamic therapy - rationale for use and possibilities in oncology, Photodynamic therapy and photodiagnostics 1, 3-7, 2014.
[3] P. Giannios, S. Koutsoumpos, K.G. Toutouzas, M. Matiatou, G.C. Zografos, and K. Moutzouris, Complex refractive index of normal and malignant human colorectal tissue in the visible and near-infrared, J. Biophotonics 10 (2), 303-310, 2017.
[4] A.B. Bucharskaya, N.I. Dikht, G.A. Afanas'eva, G.S. Terentyuk, N.B. Zakharova, G.N. Maslyakova, B.N. Khlebtsov and N.G. Khlebtsov, Saratov. Nauch.-Med. Zh.. 11, 107, 2015
[5] International Guiding Principles for Biomedical Research Involving Animals. CIOMS and ICLAS. 2012. http://www.cioms.ch/index.php/12-newsflash/227-cioms-and-iclas-release-the-newinternational-guiding-principles-for-biomedical-researchinvolving-animals
