Cytotoxic and Luminescent Properties of Novel Organotin Complexes with Chelating Antioxidant Ligand.

A novel polydentate chelating antioxidant ligand and series of organotin complexes on its base were synthesized and characterized by NMR 1H, 13C, 119Sn, IR spectroscopy, X-ray, and elemental analysis. Their antioxidant activity was evaluated in DPPH and NBT-tests, and as lipoxygenase inhibitory activity. It was shown that ligand alone is a radical scavenger, while introducing tin in the structure of the compound significantly decreases its activity. For the ligand alone the ability to strongly suppress the formation of advanced glycation end products (AGEs) was shown, which may be associated with the established antiradical activity. All synthesized compounds appeared to be moderate lipoxygenase inhibitors. The stability of compounds to hydrolysis under different pH was estimated. The ligand undergoes decomposition after about an hour, while organotin complexes on its base demonstrate vast stability, showing signs of decomposition only after 5 h of experimentation. Cytotoxicity of compounds was studied by standard MTT-test, which showed unorthodox results: the ligand itself demonstrated noticeable cytotoxicity while the introduction of organotin moiety either did not affect the toxicity levels or reduced them instead of increasing. Organotin complexes possess luminescence both as powders and DMSO solutions, its quantum yields reaching 67% in DMSO. The combination of luminescence with unique cytotoxic properties allows us to propose the synthesized compounds as perspective theranostic agents.

New Conjugates Based on AIS/ZnS Quantum Dots and Aluminum Phthalocyanine Photosensitizer: Synthesis, Properties and Some Perspectives.

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.

Synthesis of 2-chloropurine ribosides with chiral amino acid amides at C6 and their evaluation as A1 adenosine receptor agonists.

A series of purine ribonucleosides bearing chiral amino acid amides at the C6 position of 2-chloropurine was synthesized. Molecular docking of the synthesized analogs of 2-chloroadenosine by their affinity for A1 adenosine receptors (A1ARs) was conducted. The investigation of A1AR stimulating activity of synthesized nucleosides was carried out in a model of an isolated mouse atrium. We have shown that derivatives with tyrosine, valine, and serine residues exhibit the properties of A1AR partial agonists. Animal experiments in the open field test have shown that these compounds have different profiles of psychoactive action. These nucleosides have an ophthalmic hypotensive effect and reduce intraocular pressure in a manner slightly inferior to that of timolol and brimonidine. The synthesized nucleosides can be the basis for further design and synthesis of new A1AR agonists.

Fluorescence imaging analysis of distribution of indocyanine green in molecular and nanoform in tumor model.

BACKGROUND: The efficient intraoperative identification of tumors requires the development of highly specific near-infrared (NIR) probes as contrast agents. One of the most effective dyes existing in clinic oncology is Indocyanine Green (ICG). However, ICG has a rapid excretion, thus ruling out its extended accumulation in pathological tissues therefore limiting its clinical applications. ICG colloid solution (ICG NPs) consists predominantly of J-aggregates and to a lesser extent of H-aggregates and monomers. In the present study we assessed the spectral properties of ICG nanoforms in preclinical models. METHODS: We used optical spectroscopy and video fluorescence navigation to monitor accumulation and distribution of ICG monomers and ICG NPs in various tissues in mice with xenografted laryngopharyngeal carcinoma after intravenous drugs injection. RESULTS: After i.v. injection, the molecular form of ICG was not retained in the tumor and its circulation cycle averaged 5 min. Alternatively, the nanoform of the drug had a different pharmacokinetics, reaching maximum accumulation 24 h after intravenous injection. Moreover, once in the circulation, we observed a progressive accumulation in the tumor of both ICG H-aggregates and ICG monomers, but not J-aggregates. CONCLUSION: Spectral characteristics of ICG NPs indicated the presence of several fractions, namely, J- and H-aggregates along with molecular forms. These fractions had different fluorescence spectra, allowing us to track the transformation of the drug in vivo conditions. After ICG NPs administration, J-aggregates induce accumulation of monomeric forms in the tumor, enabling extended intraoperative diagnostic, and as such further studies of J-aggregates for theranostic applications in oncological surgery are of great interest.

New approaches to diagnostics and treatment of cholangiocellular cancer based on photonics methods.

Cholangiocellular cancer (CCC) is an oncological disease of the bile ducts characterized by a high mortality rate. To date, the use of standard methods for the diagnosis and treatment of CCC has not been able to reduce mortality from this disease. This work presents the results of fluorescence diagnostics (FD), which consists in using a modified optical fiber and photodynamic therapy (PDT) using a therapeutic laser instead of a low-intensity laser. This technique was tested on 43 patients in a clinical setting. The results obtained indicate a direct correlation between spectroscopic and video FD methods. Furthermore, a direct correlation was found between the photobleaching of a chlorin e6-based photosensitizer, with the commercial names of Photolon Radachlorin and Photoran and stricture regression. Our findings demonstrate the possibility of using a therapeutic laser with a wavelength of 660 nm for both diagnosis and treatment of bile ducts cancer, which results in a significant reduction of the operation time without decreasing its effectiveness.

Trials of a Fluorescent Endoscopic Video System for Diagnosis and Treatment of the Head and Neck Cancer.

This article presents the results of intraoperative fluorescent diagnostics via the endoscopic system for assessing the quality of photodynamic therapy (PDT) of head and neck cancer. The diagnosis and PDT procedures were performed on the five patients with malignant neoplasms of the vocal cords, lateral surface of the tongue, and trachea and cancer of the left parotid salivary gland. Molecular form of chlorin E6 (Ce6) was intravenously administered with a 1.0-1.1 mg/kg concentration for PDT. Fluorescent diagnostics (FD) was conducted before PDT and after PDT procedures. Control of PDT efficiency was carried out by evaluating the photobleaching of the drug (photosensitizer). The method of intraoperative fluorescent imaging allows determining the exact location of the tumor and its boundaries. The assessment of photosensitizer photobleaching in real time regime allows making quick decisions during PDT procedure, which helps improving the quality of patients' treatment. The results showed the convenience of endoscopic fluorescent video system in various nosologies of head and neck cancer. Therefore, this diagnostic approach will improve the effectiveness of cancer treatment.

Measurement of tissue optical properties in the context of tissue optical clearing.

Nowadays, dynamically developing optical (photonic) technologies play an ever-increasing role in medicine. Their adequate and effective implementation in diagnostics, surgery, and therapy needs reliable data on optical properties of human tissues, including skin. This paper presents an overview of recent results on the measurements and control of tissue optical properties. The issues reported comprise a brief review of optical properties of biological tissues and efficacy of optical clearing (OC) method in application to monitoring of diabetic complications and visualization of blood vessels and microcirculation using a number of optical imaging technologies, including spectroscopic, optical coherence tomography, and polarization- and speckle-based ones. Molecular modeling of immersion OC of skin and specific technique of OC of adipose tissue by its heating and photodynamic treatment are also discussed.