Study of antitumor efficacy and pharmacokinetics of a photosensitizer based on natural furanocoumarins and upconversion rare earth metal particles in mice with Lewis lung carcinoma and B16 melanoma

Abstract

In this work, the phototherapeutic potential of a photosensitizer containing natural furanocoumarins and upconversion microparticles NaYF₄:20 %Yb,0.25 %Tm, possessing UV luminescence, was investigated on an in vivo tumor growth model. The study included an assessment of the antitumor efficacy, pharmacokinetics and biophysical properties of the photosensitizer in mice with malignant neoplasm models (Lewis lung carcinoma and B16 melanoma). As a result of the study, a liquid form of the experimental photosensitizer was developed, which is an emulsion of furanocoumarins from the Heracleum sosnowskyi plant, which contained microparticles of NaYF₄:20 %Yb,0.25 %Tm (EmFHS-UCPs). The results of the study of the pharmacokinetics of organic and inorganic components of the EmFHS-UCPs photosensitizer substantiate the use of the intratumoral route of administration in experimental phototherapy. In mice with transplantable Lewis lung carcinoma, intratumoral injection of EmFHS-UCPs followed by laser irradiation (λ-980 nm) was shown to result in inhibition of tumor growth, tumor nodule reduction, and increased survival of tumor-bearing animals. No antitumor effect was detected in mice with B16 melanoma. An ex vivo study using tissues from experimental animals substantiated the biophysical reasons affecting the success of antitumor phototherapy using UV (365 nm) and IR (980 nm) radiation. The study showed that the degree of antitumor efficacy of emulsion furanocoumarins containing NaYF₄:20 %Yb,0.25 %Tm microparticles directly depends on the optimal route of photosensitizer administration and optical properties of tumor tissues.

Keywords: Emulsion; Furanocoumarins; Microparticles; Photosensitizer; Tumor; Upconversion.