Purpose: To develop the foundations of a new promising method of cancer magnetic-luminescent theranostics (MLT): luminescent diagnostics of tumors in the near-infrared spectral range (NIR) in combination with local ferromagnetic hyperthermia. Material and methods: For theranostics purposes, the synthesis of multifunctional nanoparticles consisting of an iron oxide core and a Lexan-polymer shell containing the ytterbium complex of hematoporphyrin IX tetramethyl ether (Yb-TME HP IX) was carried out. The study of the biodistribution and pharmacokinetics of the nanocomposite in the animals’ organs and tissues (30 female Bulb/c mice with grafted Ehrlich carcinoma) was carried out on a prototype laser-fiber fluorimeter. Results: The foundations of a new promising method of the cancer MLT have been developed: luminescent diagnostics of tumors in the NIR in combination with local ferromagnetic hyperthermia. A technique has been created for the synthesis of nanoparticles containing an iron oxide core and a polymer shell of the Lexan type, including Yb-TME HP IX. It is assumed that iron oxide nanoparticles are responsible for the local hyperthermia procedure. The inclusion of the FeOx core in composite nanoparticles allows for controlled local high frequency hyperthermia of tissues that have accumulated the nanocomposite, although it leads to a decrease in its diagnostic potential (to an approximately 2-fold decrease in the intensity of Yb-TME HP IX luminescence). However, this disadvantage can be compensated for by a slight increase in the nanocomposite therapeutic dose. Conclusion: The obtained data indicate the promise of using synthesized nanoparticles with the structure Lexan-polymer matrix + Yb-HP IX for the development of sensitive luminescent methods for diagnosing tumors of visually and endoscopically accessible localization. The size of the synthesized nanoparticles (100–200 nm) suggests the possibility of their preferential accumulation in tumor tissue due to penetration through defects in the endothelium of tumor blood vessels, as well as due to the natural tumor tropism of the porphyrin part of the complex. The use of magnetic nanoparticles in the proposed method of tumors MLT makes it possible to locally increase the intensity of the effect and reduce the frequency and magnitude of the required induction of an alternating electromagnetic field, and therefore reduce the likelihood of unwanted side effects from the field.
The dynamics of the photosensitized singlet oxygen formation for the ytterbium 2,4-di(α-methoxyethyl)deuteroporphyrin IX complex (Yb-DMDP IX) and for its metal-free form under laser excitation on a highly sensitive laser fluorimeter was studied. It has been shown that the quantum yield of singlet oxygen generation for Yb-DMDP IX (11%) is significantly lower than in the case of DMDP IX itself (40%), which experimentally confirms the low phototoxicity of the Yb complex. However, the established 11% quantum yield of 1O2 indicates the possible presence of DMDP IX in the main substance of Yb-DMDP IX, leading to residual phototoxicity. Using high-performance liquid chromatography, the quantitative ratios of the Yb-complex and its metal-free form (10%) were established. Thus, the presented Yb-complex can also be used for cancer theranostics, since after carrying out IR luminescence diagnostics (in the 900–1100 nm spectral range), it is also possible to subsequently carry out the PDT procedure in the absorption band of the porphyrin complex metal-free form at the 630 nm wavelength. The Yb-DMDP IX effectiveness for the PDT procedure can be significantly increased by treating this compound with ascorbic acid after the IR luminescence diagnostics procedure.
In this paper, we developed a promising technique for luminescent infrared (IR) diagnostics of neoplasms of visually and endoscopically accessible localization (dermatology, gynecology, dentistry) using ytterbium complexes of porphyrins. Possible mechanisms of accumulation of a pharmaceutical composition based on the ytterbium complex of 2,4-di(α-methoxyethyl)deuteroporphyrin IX (Yb-DMDP) in tumor tissues were studied. Studies on the pharmacokinetics and biodistribution of this substance in various organs and neoplasms of laboratory animals showed a significant selectivity of the accumulation of nanoparticles with ytterbium ions in tumors as early as 24 h after intravenous administration. For the purposes of luminescent IR diagnostics, a highly sensitive laser-fiber fluorimeter operating in the spectral range of 900–1100 nm was developed. Preclinical tests of the developed method of fluorescent IR cancer diagnostics were carried out and its prospects were shown.
In this paper, we developed a promising technique for luminescent infrared (IR) diagnostics of neoplasms of visually and endoscopically accessible localization (dermatology, gynecology, dentistry) using ytterbium complexes of porphyrins. Possible mechanisms of accumulation of a pharmaceutical composition based on the ytterbium complex of 2,4-di(α-methoxyethyl)deuteroporphyrin IX (Yb-DMDP) in tumor tissues were studied. Studies on the pharmacokinetics and biodistribution of this substance in various organs and neoplasms of laboratory animals showed a significant selectivity of the accumulation of nanoparticles with ytterbium ions in tumors as early as 24 h after intravenous administration. For the purposes of luminescent IR diagnostics, a highly sensitive laser-fiber fluorimeter operating in the spectral range of 900–1100 nm was developed. Preclinical tests of the developed method of fluorescent IR cancer diagnostics were carried out and its prospects were shown.
The results of the development of a small-sized laser fiber fluorimeter in the IR spectral range for a luminescent photodiagnostics of superficial localization tumors are presented. This device, working in conjunction with the “Fluroscan” type pharmaceutical composition based on the 2,4-di(α-methoxyethyl)deuteroporphyrin IX ytterbium complex dipotassium salt, ensures the achievement of high values of the luminescent diagnostic contrast index for a neoplasm/normal tissue. Import substitution of some basic design elements of the developed device, in particular the photodiode module, was carried out with a domestic analogue.
We developed a pilot version of a laser-fiber fluorimeter for luminescence diagnostics of skin and mucous membrane cancers, operating in the near-IR spectral range (9–1100 nm). The main components of the device are considered: a compact semiconductor source of laser radiation, operating at a wavelength of 405 nm; a highly sensitive optoelectronic unit; a laptop with a developed program; and a high-aperture fiber optic probe (numerical aperture up to 0.32). The device, working in conjunction with a pharmaceutical composition of the Fluroscan type based on dipotassium salt of the ytterbium complex 2,4-di(α-methoxyethyl)deuteroporphyrin IX, ensures achievement of high values of the luminescence diagnostic contrast index of neoplasm/normal tissue (up to 50 units).
In this paper we develop the fundamentals of a promising method of magnetoluminescent theranostics of tumors with visually and endoscopically accessible localization. The method is based on the use of composite nanoparticles consisting of a Lexan-type polymer matrix (nanocomposite shell) with incorporated ytterbium complexes of porphyrins (a hydrophobic ytterbium complex of hematoporphyrin IX tetramethyl ether), as well as magnetite nanoparticles. In this case, nanoparticles of the ytterbium porphyrin complex incorporated into the polymer matrix are responsible for carrying out the process of luminescent tumor diagnostics while magnetite nanoparticles provide tumor therapy through magnetic hyperthermia. The optimal size range of magnetic nanoparticles used in this method is shown to be d = 10–20 nm. Studies on the biodistribution of the nanocomposite in various organs and tumors of laboratory animals (female mice of the Bulb/c line with transplanted Ehrlich carcinoma) showed a significant selectivity of the accumulation of nanoparticles in the tumor as early as 24 h after intravenous administration.
We report the results of developing a technique for theranostics of skin neoplasms based on luminescence diagnostics in combination with photodynamic therapy (PDT) in the absorption band of porphyrin. It is shown that the therapeutic effect is achieved exclusively due to PDT, without the participation of the hyperthermia process, which occurs at temperatures above 42°C. The Fluroscan gel [based on the dipotassium salt of the ytterbium complex of 2,4-di-( α -methoxyethyl)deuteroporphyrin IX (Yb-DMDP)] is used as a preparation for theranostics. The main photophysical properties and possible mechanisms of accumulation of nanosized low-toxic photosensitisers based on this compound are studied. It is shown that the Yb-DMDP compound in a DMSO solution (30 % aqueous DMSO) enhances photophysical characteristics (luminescence lifetime 5 – 10 μs, luminescence quantum yield up to 1 %, extinction coefficient ∼1.96 × 10 5 M −1 cm −1 at a wavelength of 398 nm). Experimental animals are used to test the proposed technique for theranostics of tumours using the Fluroscan gel and a fibre-optic laser fluorimeter.
Bismuth complexes of porphyrins are of interest for IR luminescence diagnostics of cancer, since rather intense emission bands in the range of 800–920 nm have been found. In connection with the COVID-19 pandemic, bismuth compounds are also of interest in the treatment of coronavirus infection. Bismuth complexes of porphyrins of various spatial configurations have been synthesized, and several spectral-optical properties have been investigated. The influence of various substituents on the spectral characteristics was evaluated by methods of studying electronic absorption spectra, luminescence spectra, IR-, and 1 H NMR spectroscopy.
A fiber-optic laser fluorimeter operating in the near-infrared spectral range (900-1100 nm) has been developed. The fluorimeter is intended for luminescent diagnostics of skin and mucous membrane neoplasms. It uses a diagnostic agent based on the ytterbium complex of 2,4-di(α-methoxyethyl)deuteroporphyrin IX dipotassium salt. The device provides high values of the index of luminescent diagnostic contrast between neoplasm and normal tissue.
The issues of obtaining silica optical fibers with SiO2/SiO2-F composition (where SiO2 is a core, and SiO2-F is a light-reflecting cladding) with low optical losses for the near-IR spectral range are considered. This fiber type is widely used in various fields of science and technology, including laser medicine. The study results of the dependence of the numerical aperture and fluorine concentration in silica glass of the formed fiber preforms on the Freon (C3F8) consumption in the gas phase when using a waveguide-type microwave plasmotron at the H10 wavelength, are presented. It is showed that to increase the fluorimeters sensitivity in the near-IR spectral range as probe fibers for detecting luminescence, it is promising to use quartz-quartz fibers with the “Heraeus” glass core and the reflective SiO2-F cladding with an increased fluorine content in the glass (up to 7 wt. %). In this case, the numerical aperture of such fibers will reach values up to 0.32. For laser procedures in ophthalmology, surgery, phlebology and etc., optical fibers with a standard numerical aperture 0.20-0.24 can be used (with a fluorine concentration in the glass up to 3 wt. %).
A portable high-sensitivity device for recording weak luminescence signals in the near infrared (NIR) region (900–1100 nm) has been developed for applications in laser oncofluorometry. The device consists of a housing with optical lenses, interference filters, and a high-sensitivity NIR photodiode module with a preamplifier, protection circuit, and power supply. It is shown that the use of interference filters of the SL 930–1100 type can significantly increase the efficiency of the device. The use of a photodiode module unit with a sensitivity peak near 960 nm, which maximally coincides with the luminescence peak of ytterbium porphyrin complexes, ensures the sensitivity of detecting weak luminescence signals at the level of several fW.
An efficient method of gas-phase multilayer heterogeneous deposition of quartz and fluorosilicate glass in a non-isothermal plasma of a resonant local low pressure microwave discharge on quartz glass substrates and silicon wafers for the optical structures formation of waveguides and other waveguide elements based on them, is presented. It is shown that the nonisothermal plasma of a resonant local low pressure microwave discharge is an effective tool for the films formation on silicon and quartz substrates, both pure silicon dioxide and doped with fluorine. The cracks presence in films doped with fluorine is not observed even at their considerable thicknesses (20…60 µm). Deposition high rates and efficiency of silica glass doped with fluorine have been achieved (up to 7 wt.% of glass doping with fluorine at a film deposition rate of more than 3 μm/min). Planar and strip multimode and single-mode optical waveguides have been created. They are the basic structures of various fiber-optic components of local information transmission systems.
The synthesized nanoparticles based on magnetite have been investigated for magneto-luminescent theranostics of tumors. A magnetite core provides hyperthermia, IR-luminescent diagnostics due to the Yb(асас)-complex of hematoporphyrin IX tetramethyl ether is carried out. It is shown that the magnetite core inclusion doesn’t lead to a significant decrease in the luminescence intensity of the Yb-complex in the synthesized nanocomposites.
Due to the 2020 Covid-19 pandemic, bismuth compounds are of particular interest in the treatment of coronavirus infection Bismuth porphyrins complexes of various spatial configurations were synthesized The influence of various substituents on spectral characteristics was evaluated by UV-vis, luminescence spectra, IR-, 1H NMR- and X-ray photoelectron spectroscopies В связи с пандемией COVID-19 в 2020 г соединения висмута представляют особый интерес в лечении коронавирусной инфекции Так были синтезированы висмутовые комплексы порфиринов различной пространственной конфигурации Было оценено влияние различных заместителей на спектральные характеристики методами исследования электронных спектров поглощения, спектров люминесценции, ИК-, 1H ЯМР- и РФЭ-спектроскопий
The results of experimental studies on the fabrication of preforms of high aperture numerical quartz fiberoptic light guides (with a high fluorine content (up to 7 wt %) and a thickened cladding of quartz glass doped with fluorine) by the nonisothermal plasma of resonance local microwave discharge (PCVD) method are given. It is shown that by using a nonisothermal plasma of resonance local microwave discharge at low pressure, it is possible to achieve high deposition rates of fluorine-doped quartz glass layers (up to 3 μm/min) and the s/a ratio (where s is the preform diameter, a is the core diameter) at the level of 1.3 to 1.4 or higher.