Search

The creation of combined nanomedicines and their controlled release under the influence of photoinduction is an actively developing branch of scientific research. This work is devoted to the development of models of solid lipid nanoparticles for a well-known antitumor drug – gefitinib in combination with a photoindicating agent – a photosensitizer from the phthalocyanine group. Nanoparticles were obtained by several methods: hot homogenization with stearic acid, sesame oil and Tween 80 and by one-step dispersion with copolymers of lactic and glycolic acids and polyvinyl alcohol. In vitro experiments when irradiating particles with a laser in the near-infrared range (about 730 nm) proved the advantage of using combined nanoparticles with gefitinib and a photosensitizer compared to monotherapy, while the activity in terms of IC50 was 5.1-8.7 times higher for gefitinib and 1.5-1.8 times for the photosensitizer.

Abstract Cannabis producers, consumers, and regulators need fast, accurate, point‐of‐use sensors to detect Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD) from both liquid and vapor source samples, and phthalocyanine‐based organic thin‐film transistors (OTFTs) provide a cost‐effective solution. Chloro aluminum phthalocyanine (Cl‐AlPc) has emerged as a promising material due to its unique coordinating interactions with cannabinoids, allowing for superior sensitivity. This work explores the molecular engineering of AlPc to tune and enhance these interactions, where a series of novel phenxoylated R‐AlPcs are synthesized and integrated into OTFTs, which are then exposed to THC and CBD solution and vapor samples. While the R‐AlPc substituted molecules have a comparable baseline device performance to Cl‐AlPc, their new crystal structures and weakened intermolecular interactions increase sensitivity to THC. Grazing‐incidence wide‐angle X‐ray scattering (GIWAXS) and atomic force microscopy (AFM) are used to investigate this film restructuring, where a significant shift in the crystal structure, grain size, and film roughness is detected for the R‐AlPc molecules that do not occur with Cl‐AlPc. This significant crystal reorganization and film restructuring are the driving force behind the improved sensitivity to cannabinoids relative to Cl‐AlPc and demonstrate that analyte–semiconductor interactions can be enhanced through chemical modification to create more responsive OTFT sensors.

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.

Photodynamic therapy (PDT) is regarded as an alternative anti-tumor therapy which involves the administration of photosensitizers (PSs) and irradiation with specific light. However, conventional PDT therapy has been limited to the efficiency of PS delivery. A nanocarrier system could provide an effective platform for PS delivery and improve the efficiency of antitumor PDT. In this article, we prepared a complex consisting of aluminum phthalocyanine (AlPcS) and CdSe/CdZnS core-shell structure QDs and investigated the interaction between the complex and tumor cells. A more significant internalization of the conjugation was observed compared to free AlPcS via confocal fluorescence imaging. The tumor cells exhibited an obvious apoptotic trend after QD–AlPcS-mediated PDT.

Today, fluorescent diagnostics and photodynamic therapy are promising methods for diagnosing and treating oncological diseases. The development of new photosensitizers (PS) is one of the most important tasks to improve the efficiency of both laser-induced diagnostics and therapy. In our study, we conjugated PS with AIS/ZnS triple quantum dots (QDs) to obtain non-aggregated complexes. It was shown that the conjugation of PS with QDs does not change the PS fluorescence lifetime, which is a marker of the preservation of PS photophysical properties. In particular, efficient resonant Förster energy transfer (FRET), from QDs to PS molecules in the conjugate, increases the PS luminescence response. The FRET from QD to PS molecules with different ratios of donor and acceptors are shown. It has been demonstrated that the average efficiency of FRET depends on the ratio of PS and QD and reaches a maximum value of 80% at a ratio of 6 PS molecules per 1 QD molecule. Thus, these studies could help to contribute to the development of new complexes based on QD and PS to improve the efficiency of phototheranostics.

The study of phthalocyanines, known photosensitizers, for biomedical applications has been of high research interest for several decades. Of specific interest, nanophotosensitizers are crystalline aluminum phthalocyanine nanoparticles (AlPc NPs). In crystalline form, they are water-insoluble and atoxic, but upon contact with tumors, immune cells, or pathogenic microflora, they change their spectroscopic properties (acquire the ability to fluoresce and become phototoxic), which makes them upcoming agents for selective phototheranostics. Aqueous colloids of crystalline AlPc NPs with a hydrodynamic size of 104 ± 54 nm were obtained using ultrasonic dispersal and centrifugation. Intracellular accumulation and localization of AlPc were studied on HeLa and THP-1 cell cultures and macrophages (M0, M1, M2) by fluorescence microscopy. Crystallinity was assessed by XRD spectroscopy. Time-resolved spectroscopy was used to obtain characteristic fluorescence kinetics of AlPc NPs upon interaction with cell cultures. The photodynamic efficiency and fluorescence quantum yield of AlPc NPs in HeLa and THP-1 cells were evaluated. After entering the cells, AlPc NPs localized in lysosomes and fluorescence corresponding to individual AlPc molecules were observed, as well as destruction of lysosomes and a rapid decrease in fluorescence intensity during photodynamic action. The photodynamic efficiency of AlPc NPs in THP-1 cells was almost 1.8-fold that of the molecular form of AlPc (Photosens). A new mechanism for the occurrence of fluorescence and phototoxicity of AlPc NPs in interaction with cells is proposed.

Early diagnosis of caries and tooth enamel microcracks is of great importance for preventing the destruction of healthy tooth enamel. Inorder to detect microcracks in the enamel and pathogenic microflora foci that can cause caries, nanoform of aluminum phthalocyanine (AlPc) can be used as a marker. In a colloidal solution, the nanoparticles do not fluoresce, unlike their molecular form. To convert the particle into its molecular form, it is necessary to have a solvent or specific environment (bacteria, macrophages, etc.). That is why the hydrophobic nanoparticles of aluminum phthalocyanine (nAlPc) can act as markers for detecting hidden pathogenic microflora during fluorescent diagnostics. Further reduction of the diagnosis time and increase the efficiency can be achieved by using biologically compatible surfactants as additional activators of nAlPc.In order to carry out local fluorescence spectroscopy of enamel microcracks and pathogenic microflora foci on the enamel surface, a model compound containing surfactants, auxiliary components and nAlPc colloid at a concentration of 10 mg/l was prepared.Studies on the interaction of the model compound with nAlPc and Protelan MST-35 with tooth enamel ex vivo have shown this surfactant to be a promising auxiliary activator of the nanoparticles, allowing conducting local fluorescence spectroscopy of the tooth enamel surface 3 min after application. In addition, statistical processing of the results showed the effectiveness of using the model compound for local fluorescence spectroscopy of the enamel surface in order to detect the enamel microcracks and the pathogenic microflora accumulation foci that can lead to the development of a cariogenic process.

The development and the spectral research of unique coating as crystalline nanoparticles of IR photosensitizers were performed for the creation of hydroxyapatite implants with photobactericidal properties. It has been proved that by the interaction of nanoparticles covering implant with the polar solvent, which simulates the interaction of the implant with the biocomponents in vivo (fast proliferating and with immunocompetent cells), photosensitizers nanoparticles change the spectroscopic properties, becoming fluorescent and phototoxic. Thus, the developed coating based on crystalline photosensitizer nanoparticles with studied specific properties should have antibacterial, anti-inflammatory effect by the photodynamic treatment in the near implant area. This research opens the prospect of the local prevention of inflammatory and autoimmune reactions in the area of implantation. The results of the study suggest a promising this technology in order to create implants with photobactericidal properties.

This work is dedicated to the study of the photoluminescence kinetics of aluminum phthalocyanine nanoparticles in colloidal solutions at different pH and in the interaction with immune cells (macrophages). For measurements we used a registration system based on Hamamatsu streak camera (C10627-13 Hamamatsu Photonics) with picosecond temporal resolution (15 ps), conjugated with the fiberoptic spectrometer and picosecond laser pumping. The changes in fluorescence decay kinetics as additional lifetime components of fluorescence were found during the experiment. The number of components and duration of lifetimes changed while interacting with cells and depends on pH. At pH 2 the presence of two fluorescence lifetimes was recorded: the first one was 5 ns, which corresponded to the molecular form in solution, and 1.5 ns, which corresponded to bound state of phthalocyanine molecules. Due to the absence of other possible objects for bounding in the solution except of the nanoparticles we can suggest with a high degree of accuracy that the bounding occurs with the very these nanoparticles. Analysis of the fluorescence lifetimes of aluminum phthalocyanine nanoparticles in macrophages indicated the presence of two components: 9 ns and 4.5 ns. A model of surface molecules transitions from parallel to perpendicular position, regarding to the plane of the crystal nanoparticle was proposed.