Mikhail A. Grin’s research while affiliated with MIREA - Russian Technological University and other places

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Publications (67)


Figure 2. The dose-dependent biodistribution of [ 99m Tc]Tc-HYNIC-Chl (injected doses of 1.2 mg/kg, 6 mg/kg, and 12 mg/kg) in Nu/j mice bearing A-431 (epidermoid cancer tumor) xenografts at 2 h post injection (pi). Data are presented as mean %ID/g ± SD for four animals. Data for the rest of the gastrointestinal tract with contents (GI tract) and the rest of the body are presented as %ID per whole sample. The symbol «*» marks a significant difference between groups (p < 0.05, one-way ANOVA), and the symbol «ns» marks an insignificant difference between groups (p > 0.05, one-way ANOVA).
Radiochemical yield from radiolabeling optimization studies, isolated yield, radiochemical purity, and maximum molar activity of HYNIC-Chl radiolabeled with [ 99m Tc]TcO 4 − .
Novel Chlorin with a HYNIC: Synthesis, 99mTc-Radiolabeling, and Initial Preclinical Evaluation
  • Article
  • Full-text available

December 2024

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20 Reads

Molecules

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Nikita Suvorov

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Mikhail Grin

The use of radiopharmaceuticals for diagnostics in oncology allows for the detection of the disease at an early stage. Among diagnostic radionuclides, 99mTc is a promising isotope that has been used to create several drugs for clinical use. One of the most effective 99mTc chelators is 6-hydrazinylnicotinic acid (HYNIC), which, when combined with various vector molecules, can be used for targeted delivery of radionuclides to tumor tissues. At the same time, it is known that tetrapyrrole macrocycles are capable of selective accumulation in tumors, and thus can be used to target radiopharmaceuticals with 99mTc. In this work, the conjugate of natural chlorin and HYNIC was obtained, and preliminary preclinical studies were carried out on its radiocomplex with 99mTc.

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Estimated interaction energies of ligands and DNA.
Antitumor efficiency of different therapy schedules for M-1 sarcomas in rats.
Conjugate of Natural Bacteriochlorin with Doxorubicin for Combined Photodynamic and Chemotherapy

June 2024

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56 Reads

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1 Citation

International Journal of Molecular Sciences

Chemotherapy is among the main classical approaches to the treatment of oncologic diseases. Its efficiency has been comprehensively proven by clinical examinations; however, the low selectivity of chemotherapeutic agents limits the possibilities of this method, making it necessary to search for new approaches to the therapy of oncologic diseases. Photodynamic therapy is the least invasive method and a very efficient alternative for the treatment of malignant tumors; however, its efficiency depends on the depth of light penetration into the tissue and on the degree of oxygenation of the treatment zone. In this work, a hitherto unknown conjugate of a natural bacteriochlorin derivative and doxorubicin was obtained. In vitro and in vivo studies showed a more pronounced activity of the conjugate against MCF-7 and 4T1 cells and its higher tumorotropicity in animal tumor-bearing animals compared to free anthracycline antibiotic. The suggested conjugate implements the advantages of photodynamic therapy and chemotherapy and has great potential in cancer treatment.




Figure 5. (A) Absorption spectra of an ETH·HCl solution in Kolliphor ELP in PSS with predominance of the E (in the dark) and Z (after irradiation with 365 nm light) isomers. (B) Time dependence of ln(Cₜ/C₀) plotted in linearized coordinates.
Studies of the solubilization conditions of ethercaine.
Local anesthetic activity of ethercaine on rabbit eye cornea according to the Regnier method.
Development of a Dosage form for a Photoswitchable Local Anesthetic Ethercaine

October 2023

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181 Reads

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3 Citations

Pharmaceuticals

The toxicity of local anesthetics is a serious problem, given their widespread use. One of the main causes of the side effects of local anesthetics is their non-selectivity of action in the body. A possible way to increase the selectivity of the action of drugs is to use the photopharmacology approach. Previously, we described the light-controlled local anesthetic ethercaine, the biological effect of which can be controlled using light, thereby increasing its selectivity of action. An important limitation of ethercaine was its low solubility in water, limiting the potential of this compound. In this work, we developed a dosage form of ethercaine, which allowed us to increase its solubility from 0.6% to 2% or more. The resulting 1% solution of ethercaine hydrochloride in 4% Kolliphor ELP had high biological activity on the surface anesthesia model, while demonstrating low acute toxicity in mice with intravenous administration (4–5 times less than that of lidocaine).


Characteristics of included studies-randomized controlled trials.
Cont.
Risk of bias of randomized clinical trials, assessed through the ROB2 tool [35].
Effectiveness of Photodynamic Therapy as Antiseptic Measure for Oral Cavity and Pharynx: A Systematic Review

August 2023

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83 Reads

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1 Citation

Dentistry Journal

Background: The complex traditional treatment of inflammation diseases in oral cavity includes the prescription of antibiotic and antiseptic therapy. This systematic review aims to evaluate the effect of photodynamic therapy as a part of management of inflammatory diseases in oral cavity; Methods: The study is presented in accordance with the preferred reporting points for systematic reviews and meta-analyses (PRISMA). This systematic review was conducted using electronic databases such as Medline PubMed, Scopus and the Cochrane Central Register of Controlled Trials. All the studies in this systematic review, were randomized, the risk of bias 2 (ROB 2) were assessed; Results: Considering the inclusion and exclusion criteria, we included 10 randomized clinical trials, published up to 2023 investigating the application of photodynamic therapy as a part of management of inflammatory diseases in oral cavity. The diode laser was used in the oral cavity in the zone of inflammatory process (gingivitis, mucositis, periimplantitis, marginal periodontitis, abscess, periostitis, osteomyelitis etc.) in nine studies or in the zone before surgical procedures in one study; Conclusion: Based on the results of clinical studies, it can be stated that photodynamic therapy shows good results for operations performed in the oral cavity and pharynx.


Scheme 3. Scheme for the interaction of Lawesson's reagent with ketones of pyropheophorbide a.
Thionation conditions.
Thiocarbonyl Derivatives of Natural Chlorins: Synthesis Using Lawesson’s Reagent and a Study of Their Properties

May 2023

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228 Reads

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3 Citations

Molecules

The development of sulfur-containing pharmaceutical compounds is important in the advancement of medicinal chemistry. Photosensitizers (PS) that acquire new properties upon incorporation of sulfur-containing groups or individual sulfur atoms into their structure are not neglected, either. In this work, a synthesis of sulfur-containing derivatives of natural chlorophyll a using Lawesson’s reagent was optimized. Thiocarbonyl chlorins were shown to have a significant bathochromic shift in the absorption and fluorescence bands. The feasibility of functionalizing the thiocarbonyl group at the macrocycle periphery by formation of a Pt(II) metal complex in the chemotherapeutic agent cisplatin was shown. The chemical stability of the resulting conjugate in aqueous solution was studied, and it was found to possess a high cytotoxic activity against sarcoma S37 tumor cells that results from the combined photodynamic and chemotherapeutic effect on these cells.


Potential agents for combined photodynamic and chemotherapy in oncology based on Pt(II) complexes and pyridine-containing natural chlorins

March 2023

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125 Reads

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3 Citations

Journal of Porphyrins and Phthalocyanines

Combined therapy is currently a popular method for increasing the efficiency of antitumor treatment. It involves the use of two different tumor treatment methods, namely, chemotherapy and PDT. Combining a cytotoxic agent and a photosensitizer in a single molecule results in a synergistic antitumor effect that overcomes the multiple drug resistance and reduces the therapeutic drug doses. In this work, pyridine-containing natural chlorins were obtained by introducing a pyridine group into 13 ¹ -[Formula: see text]-(4-aminobutyl)amide of chlorin [Formula: see text] and its bacteriochlorin analogue, [Formula: see text]-propyloxime-[Formula: see text]-propoxybacteriopurinimide as well as [Formula: see text]-aminobacteriopurinimide methyl ester. Moreover, a terpyridine residue was introduced as an external chelating moiety into [Formula: see text]-hydroxypurpurinimide and [Formula: see text]-aminobacteriopurinimide, and platinum complexes of all the above photosensitizers were obtained. The interactions of the latter with DNA were simulated and the lead compound, the platinum complex of pyridine derivative 13 ¹ -[Formula: see text]-(4-aminobutyl)amide chlorin [Formula: see text], which may become a potential agent for combined photodynamic and chemotherapy in oncology, was selected. The ability of the compounds obtained to manifest photodynamic and chemocytotoxic effects on tumor cells of various genesis was shown.



Figure 1. Strategy for the synthesis of conjugates.
Figure 2. Absorption and electronic fluorescence spectra of dipropoxy-BPI 5; amino acid modifications 6a,b; NHC-compounds 7a,b and metal complexes 8a,b.
Figure 5. Photoinduced antitumor activity of NHC-derived dipropoxy-BPI with histamine (7b)-(B) and its metal complex with Au (I) (8b)-(C) versus dipropoxy-BPI (5)-(A) in mice with PC-3 adenocarcinoma xenografts. ITG was calculated in comparison to the "Control-dark" group-(D); KP-(E). The compound doses were counted as 1.0 mg/kg. The time interval between injection and irradiation lasted 15 min. Radiation source wasALHT-ELOMED laser device (Elomed, Dubna, Russia) for PDT, 810 nm, 100 mW/cm 2 power density, 90 J/cm 2 energy density. The animals were observed for 30 days. Animals of the control group were injected with 0.9% NaCl. *-p ≤ 0.05.
Scheme 2. Reagents and conditions: i: 1. CH2Cl2, EDC, NHS, 0 °C, 1 h, 2. histamine hydrochloride, Et3N, 36 h, ii: 1. CH2Cl2, EDC, NHS, 0 °C, 1 h, 2. histidine methyl ester dihydrochloride, Et3N, 36 h, Ar, iii: CH3I 8% in CH3CN, K2CO3, 70 °C, Ar, 16 h.
Cytotoxic activity of compounds in vitro.
N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer

December 2022

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88 Reads

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6 Citations

International Journal of Molecular Sciences

Photodynamic therapy (PDT) is currently regarded as a promising method for the treatment of oncological diseases. However, it involves a number of limitations related to the specific features of the method and the specific characteristics of photosensitizer molecules, including tumor hypoxia, small depth of light penetration into the tumor tissue, and low accumulation sensitivity. These drawbacks can be overcome by combining PDT with other treatment methods, for example, chemotherapy. In this work, we were the first to obtain agents that contain bacteriopurpurinimide as a photodynamic subunit and complexes of gold(I) that implement the chemotherapy effect. To bind the latter agents, N-heterocyclic carbenes (NHC) based on histidine and histamine were obtained. We considered alternative techniques for synthesizing the target conjugates and selected an optimal one that enabled the production of preparative amounts for biological assays. In vitro studies showed that all the compounds obtained exhibited high photoinduced activity. The C-donor Au(I) complexes exhibited the maximum specific activity at longer incubation times compared to the other derivatives, both under exposure to light and without irradiation. In in vivo studies, the presence of histamine in the NHC-derivative of dipropoxy-BPI (7b) had no significant effect on its antitumor action, whereas the Au(I) metal complex of histamine NHC-derivative with BPI (8b) resulted in enhanced antitumor activity and in an increased number of remissions after photodynamic treatment.


Citations (53)


... Both pathways contribute to PDT's therapeutic effects, including the direct destruction of cancer cells, blood vessel closure, and the stimulation of the host immune system [15]. Efficient PDT requires photosensitizers with redox properties that allow them to participate in both photochemical mechanisms, but at the same time are sufficiently photostable, to generate ROS with high efficiency [16][17][18][19][20]. ...

Reference:

One Change, Many Benefits: A Glycine-Modified Bacteriochlorin with NIR Absorption and a Type I Photochemical Mechanism for Versatile Photodynamic Therapy
Conjugate of Natural Bacteriochlorin with Doxorubicin for Combined Photodynamic and Chemotherapy

International Journal of Molecular Sciences

... It possesses antioxidant, antigenotoxic, and antimutagenic properties [7][8][9]. Its derivatives are bioactive and easily modified, and their synthesis cost is low [5,10,11]. Industrial forms of chlorophyll are well known, and they are successfully used in the food industry, in cosmetics, and in medicine [9,12]. ...

Thiocarbonyl Derivatives of Natural Chlorins: Synthesis Using Lawesson’s Reagent and a Study of Their Properties

Molecules

... PDT has emerged as an important alternative treatment for various advanced cancers due to its ability to improve survival rates without compromising patients' quality of life. However, challenges remain such as insufficient light penetration depth limiting therapeutic effectiveness against deep-seated tumors, difficulties in controlling laser parameters, and suboptimal synergy among various chemotherapeutic agents during combination therapies [30,31]. Accumulating more clinical data will be essential for addressing these challenges moving forward. ...

Potential agents for combined photodynamic and chemotherapy in oncology based on Pt(II) complexes and pyridine-containing natural chlorins
  • Citing Article
  • March 2023

Journal of Porphyrins and Phthalocyanines

... The primary goal is to enhance efficiency by minimizing aggregation at the intended site. Porphyrin may accumulate in healthy tissues, leading to potential damage [156,157]. To address these challenges, nanoparticles can be utilized to enhance the biocompatibility of porphyrin. ...

Synthesis Strategy of Tetrapyrrolic Photosensitizers for Their Practical Application in Photodynamic Therapy

Macroheterocycles

... Despite its high efficiency, DOX, like all anthracycline antibiotics, has the very serious drawback of low selectivity and specificity for a tumor, which results in the development of serious adverse reactions including damage to many organs and tissues. Cardiotoxicity is a limiting factor that prevents the escalation of a cytostatic dose, and hence, attainment of high efficiency [33]. To overcome the considered limitations, a conjugate of bacteriochlorin and DOX was prepared (PS+DOX). ...

N-Heterocyclic Carbenes and Their Metal Complexes Based on Histidine and Histamine Derivatives of Bacteriopurpurinimide for the Combined Chemo- and Photodynamic Therapy of Cancer

International Journal of Molecular Sciences

... In the last couple of decades, major progress has been made in the synthesis, characterization, and application of fluorescent materials, along with the development of nano-, bio-based, sensor, imaging and high-performance-material-based technologies, which is believed to contribute to the extension of their applications in bio-sensing, bio-labeling, bio-tracing, bio-imaging, disease diagnosis and therapy, etc. Biocompatibility is the top priority when fluorescent materials are used in bio-fields; a great number of biocompatible fluorescent materials (BFMs) have been obtained, such as organic small-molecule dyes, fluorescent conjugated polymers, metal nanoclusters, rare earth ion-based nanoparticles (e.g., rare-earth-doped upconversion nanoparticles), quantum dots, carbon nanomaterials (e.g., carbon nanotubes and carbon nanodots) and various fluorescent proteins. This Special Issue, "Fluorescent Materials with Excellent Biocompatibility and Their Application in Bio-Sensing, Bio-Imaging", includes twelve research articles covering biosensors based on ion sensors, the detection of pathological oxidative stress and disease detection [1][2][3][4][5][6][7][8][9][10][11][12], as well as four review articles focused on different types of fluorescent probes and biological applications [13][14][15][16]. ...

A New Glutathione-Cleavable Theranostic for Photodynamic Therapy Based on Bacteriochlorin e and Styrylnaphthalimide Derivatives

Biosensors

... Similarly to bacteriochlorins [46], the intracellular distribution of PS+DOX occurs in both types of cells; similar intracellular distributions of the compound are observed: accumulation in vesicular structures, intense diffuse staining of the cytoplasm, and much weaker staining of the nuclei. ...

Photodynamic Properties of Lysine and Arginine Derivatives of Bacteriopurpurinimide
  • Citing Article
  • November 2022

... The study findings demonstrated that early consistent exercise may improve the anti-inflammatory immune response in middle-aged male mice via epigenetic modulation of immune metabolism. The hepatic production of pipecolic acid is pivotal (Vlasova et al., 2022), being intricately linked to fatty acid synthase and fatty acid desaturase, and constitutes a significant component of the lipid metabolism route. Insufficient pipecolic acid can result in fatty acid oxidation disorder, bile acid synthesis defect, and long-chain fatty acid transport deficiency, culminating in lipid metabolism problem. ...

Liposomal Form of 2,4-Dinitrophenol Lipophilic Derivatives as a Promising Therapeutic Agent for ATP Synthesis Inhibition

... This feature of biodistribution forms the basis for the use of these compounds in photodynamic therapy and fluorescence diagnostics of cancer as photosensitizers [22][23][24]. A special place among these compounds is occupied by derivatives of natural chlorophyll A, which exhibit high selectivity of accumulation in tumor tissues and lack toxic effects on the body due to their rapid biodegradability [25,26]. ...

Advantages of combined photodynamic therapy in the treatment of oncological diseases

Biophysical Reviews

... Photosensitizers (PS) based on bacteriochlorophyll a derivatives, in particular, bacteriopurpurinimides (BPI) that absorb radiation in the 800 nm range, are promising agents for photodynamic therapy (PDT), which we are actively studying, including the synthesis of amino acid derivatives of BPI and their metal complexes as agents with combined antitumor action [25,26]. ...

Guanidine and Biguanidine Derivatives of Natural Chlorins: Synthesis and Biological Assessment
  • Citing Article
  • January 2021

Macroheterocycles