ORIGINAL ARTICLES
In recent years, the development of methods of photodynamic therapy (PDT) and photodynamic photodiagnostics (PD) in Russia is characterized by an intensive rise, steadily growing interest of specialists from various medical specialties in the method of specialists from various medical specialties, an increase in the level of equipment number of hospitals with the necessary equipment for performing PD and PDT, the and the emergence of new photosensitizers on the pharmaceutical market, and an increasing increase in the level of patients’ confidence in these methods. This study analyzes the dynamics of the development of the clinical application and scientific developments of PD and PDT over the past decade in Russia in terms of the volume of public procurement of photosensitizers, as well as the activity of research work in the field of PD and PDT, the number of candidate and doctoral dissertations theses on this topic and the number of scientific publications in the RSCI. 688 contracts for the supply of photosensitizers for clinical use were analyzed. The analysis showed a stable annual growth in the volume of public procurement of photosensitizers, an increase in the number of subjects of the Russian Federation and clinical centers that purchase photosensitizers through the portal www.zakupki.gov.ru. From 2014 to 2020, the total volume of public procurement of all photosensitizers increased by 8 times (from 36.42 million rubles (3.58 thousand packages) to 307.37 million rubles (18.99 thousand packages)). The annual increase in the volume of public procurement in numerical terms over the previous 6 years ranged from 9.4% to 63.2% in different years. The main share of state purchases of photosensitizers falls on Moscow and St. Petersburg, h. However, in recent years there has been a noticeable trend towards an increase in sales of photosensitizers in the regions. Thus, in recent years, the share of purchases of photosensitizers in the constituent entities of the Russian Federation with a population of less than 1 million people has significantly increased (from 2.9% of the total number of purchases in 2014 to 25.3% in 2020). Also, in recent years, there has been a significant increase in the activity of research work activity in the field of PD and PDT. The number of defended candidate and doctoral dissertations theses defended in the field of PD and PDT photodynamic therapy and fluorescent diagnostics has been steadily high in recent years and, in some scientific specialties, reaches 2-3% of the total number of defended dissertations theses defended in these specialties. The increase in the total number of publications over 10 years according to the RSCI was 224% (from 218 publications in 2014 to 489 publications in 2019), according to the RSCI. The results obtained confirm the growing demand for photosensitizers for photodynamic therapy and fluorescence diagnostics in clinical practice, the expansion of the geography of the use of methods, as well and the stable interest in this topic in the research environment.
Today, photodynamic therapy is one of the most promising minimally invasive methods of treatment of various diseases, including cancer. The main limitation of this method is the insufficient penetration into the tissue of laser radiation used to activate photosensitizer molecules, which makes it difficult to carry out therapy in the treatment of large or deep-seated tumors. In this regard, there is a great interest in the development of new strategies for photodynamic therapy using infrared radiation for excitation, the wavelengths of which fall into the “transparency window” of biological tissues. In this work, it was proposed to use upconversion NaGdF4 :Yb:Er nanoparticles (UCNP), which absorb infrared excitation and serve as a donor that transfers energy to the photosensitizer. Photosens and phthalosens were chosen as the most promising photosensitizers for the study. The aim of this work was to study the energy transfer processes between upconversion nanoparticles doped with rare-earth ions and photosensitizer molecules. in order to excite photosensitizers with IR radiation and carry out photodynamic therapy of deep-seated neoplasms. Using spectroscopic and time-resolved methods, it has been demonstrated that there is an efficient energy transfer between upconversion particles and photosensitizers phthalosens and photosens. The calculated efficiency of energy transfer by the Foerster mechanism was 41% for the UCNP + photosens system and 69% for the UCNP + phthalosens system. It has been experimentally and theoretically proved that there is a binding of photosensitizer molecules with UCNP by means of surfactants, leading to a reduction in the distance between them, due to which effective nonradiative energy transfer is realized. The generation of singlet oxygen by the phthalosens photosensitizer upon excitation by means of energy transfer from UCNP, excited at 980 nm wavelength of, has been demonstrated.
Intraoperative fluorescence diagnostics of high-grade gliomas is widely used in neurosurgical practice. This work analyzes the possibilities of fluorescence diagnostics for low-grade gliomas (LGG) using chlorin e6 photosensitizer. The study included patients with newly diagnosed LGG, for whom chlorin e6 was used for intraoperative fluorescence control at a dose of 1 mg/kg. During the operation, the fluorescence intensity of various areas of the putative tumor tissue was analyzed using the RSS Cam – Endo 1.4.313 software. Tissue samples with various degrees of fluorescence intensity were compared with the results of their histopathological analysis (WHO tumor diagnosis, Ki-67 index, P53, VEGF). Fluorescence was detected in more than half of the cases, but in most cases had a focal character and low fluorescence intensity. The fluorescence intensity directly correlated with the data of histopathological examination of tumor tissues (Ki-67 index (p=0.002), expression of P53 (p=0.0015) and VEGF (p=0.001)). The sensitivity of the method for LGG surgery was 72%, the specificity was 56,7%. Intraoperative fluorescence diagnostics with chlorin e6 can be used in LGG surgery, especially to visualize intratumoral areas with a higher degree of anaplasia.
Nanoparticles are used as drug carriers to increase the selectivity and effectiveness of therapy, as well as for combined therapy that utilizes different effects. Iron oxide nanoparticles are promising in this aspect. Due to magnetic properties, they can be used as a contrast agent for magnetic resonance imaging. Also, iron oxide nanoparticles could be coated with a photosensitizer for photodynamic therapy and their laser or magnetic heating can be used for phototherapy. Local enhancement of the electromagnetic field near iron oxide nanoparticles can increase the fluorescence intensity of photosensitizers and the efficiency of singlet oxygen generation. This paper presents the results of a study of iron oxide nanoparticles focused on the photophysical aspects of the formation of “hot spots” under laser irradiation. The photoinduced effects of iron oxide nanoparticles observed in in vitro experiments lead to the rupture of lysosomes. Theoretical modeling showed that the heating of iron oxide nanoparticles with a radius of 35 nm under the action of laser radiation is about 89°C and 19°C for wavelengths of 458 and 561 nm, respectively. Local field enhancement occurs in pairs of nanoparticles of various sizes and strongly depends on the distance between them. The maximum gain is achieved at small distances between nanoparticles. For a dimer of nanoparticles with radii of 10 and 35 nm at a distance of 1 nm, an enhancement factor of two orders of magnitude was obtained. The investigated phenomenon of «hot spots» is in demand for precision therapy, because the photo-induced processes occur at small distances between nanoparticles, in areas of their high accumulation.
LITERATURE REVIEWS
The paper presents the results of literature data analysis on the main directions of precancerous diseases of the cervix uteri and cervical cancer treatment. Side effects following surgery or radiation treatment can lead to structural deformities, scarring, hyperpigmentation, systemic side effects, and destruction of normal tissue. In addition, the use of traditional methods of treatment can cause multidrug resistance, which will lead to ineffective treatment and the development of a relapse of the disease. To avoid toxicity and reduce side effects, alternative treatment strategies have been proposed. Photodynamic therapy (PDT) is a promising organ-preserving highly selective method for treating cervical neoplasia, which includes two stages: the introduction of a photosensitizer and local exposure to directed light radiation. A number of studies have demonstrated the high clinical efficacy of this method in the treatment of patients with cervical neoplasia and carriage of human papillomavirus infection without adverse consequences for fertility. The use of PDT contributes to the successful outcome of the treatment of pathological foci on the mucous membrane of the cervix, the effectiveness and safety of the method is ensured by the selective effect on tissues. In the course of treatment, normal surrounding tissues are not damaged, there is no gross scarring and stenosis of the cervical canal, thereby PDT allows maintaining the normal anatomical and functional characteristics of the cervix.
CASE-REPORTS
The article presents a clinical observation. The patient, 72 years old, applied to the MNII them. P.A. Herzen with complaints about the presence of an ulcerated tumor of the left ear. After further examination, a diagnosis was made - basal cell carcinoma of the ear skin with spread to the skin of the parotid region T3N0M0. On July 9, 2021, the patient underwent a course of photodynamic therapy (PDT) using a photosensitizer based on chlorin e6 and a diode laser with a wavelength of 662 nm. After one course of PDT, complete regression of the tumor was recorded.