Aurumacryl is an incomplete metal salt of poly(acrylic acid) that exhibits hemostatic activity and inhibits the growth of transplantable carcinomas in vivo. The samples of aurumacryl synthesized following the original technique are insufficiently soluble, which complicates the study of the mechanisms involved in their synthesis and underlying their cytotoxic effect. The aim of this work was to study the impact of the following factors on aurumacryl properties: the molecular weight of the polyacrylate polymer in a range between 2 and 1,000 kDa, the presence of a counterion H+ or Na+, the molar ratio of AuCl– to the polyacrylate polymer (1 : 5 and 1 : 10), the total concentration of the polyacrylate polymer during synthesis (0.1 and 3%), and the type of drying (lyophilization). By comparing the cytotoxicity of aurumacryl samples with significantly different molar ratio of gold ions to the polyacrylate polymer against human breast carcinoma cells (MCF-7), we established that the proportion of the polymer and its molecular weight in the sample do not affect the biological properties of the synthesized substance. Using UV spectroscopy, we revealed that the concentration of Au (III) ions in aurumacryl determines its cytotoxicity.
The novel metal (Cr, Mo, W, Re) carbonyl complexes with porphyrin and carborane isocyanide ligands were prepared as potent conjugates for combined photodynamic and photoinducible CO-releasing antitumor agents.
Abstract Magnetosensitive nanogel based on polyacrylic acid, N ‐isopropylacrylamide, and magnetic nanoparticles containing Fe 3+ is obtained. The size and morphology of the magnetic nanogel are determined. The size and magnetic characteristics of the inorganic phase are established. The anticancer properties of magnetic nanogel loaded by doxorubicin are studied.
Copper-containing agents are promising antitumor pharmaceuticals due to the ability of the metal ion to react with biomolecules. In the current study, we demonstrate that inorganic Cu2+ in the form of oxide nanoparticles (NPs) or salts, as well as Cu ions in the context of organic complexes (oxidation states +1, +1.5 and +2), acquire significant cytotoxic potency (2-3 orders of magnitude determined by IC50 values) in combinations with N-acetylcysteine (NAC), cysteine, or ascorbate. In contrast, other divalent cations (Zn, Fe, Mo, and Co) evoked no cytotoxicity with these combinations. CuO NPs (0.1-1 µg/mL) together with 1 mM NAC triggered the formation of reactive oxygen species (ROS) within 2-6 h concomitantly with perturbation of the plasma membrane and caspase-independent cell death. Furthermore, NAC potently sensitized HCT116 colon carcinoma cells to Cu-organic complexes in which the metal ion coordinated with 5-(2-pyridylmethylene)-2-methylthio-imidazol-4-one or was present in the coordination sphere of the porphyrin macrocycle. The sensitization effect was detectable in a panel of mammalian tumor cell lines including the sublines with the determinants of chemotherapeutic drug resistance. The components of the combination were non-toxic if added separately. Electrochemical studies revealed that Cu cations underwent a stepwise reduction in the presence of NAC or ascorbate. This mechanism explains differential efficacy of individual Cu-organic compounds in cell sensitization depending on the availability of Cu ions for reduction. In the presence of oxygen, Cu+1 complexes can generate a superoxide anion in a Fenton-like reaction Cu+1L + O2 → O2-. + Cu+2L, where L is the organic ligand. Studies on artificial lipid membranes showed that NAC interacted with negatively charged phospholipids, an effect that can facilitate the penetration of CuO NPs across the membranes. Thus, electrochemical modification of Cu ions and subsequent ROS generation, as well as direct interaction with membranes, represent the mechanisms of irreversible membrane damage and cell death in response to metal reduction in inorganic and organic Cu-containing compounds.
By using NGS-sequencing libraries of DNA from periodontal swabs with primers specific to V6 region of 16S rDNA prevalence of bacterial genera and species in periodontal and colonic microbiota of patients with periodontitis of different severity and healthy donors was analyzed. Hyper-colonization of the colon with Akkermansia muciniphila was found to be the most important maker of negative predisposition to periodontitis (t=133,7 at р=10(-6)). This result is in a good agreement with communications about positive impact of hyper-colonization of the colon with this species on type 2 diabetes, obesity, atopic dermatitis, and antibiotic-induced diarrhea associated with Clostridium dificile. Analysis of the periodontal protectors at the periodontium elucidated a number of close taxonomic relatives of the periodontal pathogens by Socransky, e.g. Aggregatibacter segnis and Aggregatibacter aphrophilus are closely related to Aggregatibacter actinomycetemcomitans; Treponema vencentii is a relative of Treponema denticola; Prevotella baroniae, Prevotella salivae and Prevotella spp. are relatives of Prevotella intermedia; Campylobacter concisus is a relative of Campylobacter jejuni, causative agent of enterocolitis.В работе с применением метода NGS-секвенирования банков суммарной ДНК содержимого пародонтальных карманов с праймерами на область V6 16S рДНК проанализирован качественный и количественный состав видов и родов бактерий в микрофлоре пародонта и кишечника пациентов с пародонтитом разной степени тяжести и лиц со здоровым пародонтом. Важным маркером отсутствия предрасположенности к пародонтиту оказалось повышенное содержание в кишечнике Akkermansia muciniphila (t=133,7 при р=10–6). Данный результат коррелирует с сообщениями о влиянии этой бактерии на риск развития диабета, ожирения, атопического дерматита и постантибиотической диареи, ассоциированной с Clostridium dificile. При анализе пародонтопротекторов, населяющих сам пародонт, выявлен ряд таксономических родственников патогенов по Сокранскому: Aggregatibacter segnis и Aggregatibacter aphrophilus (родственники A. actinomycetemcomitans), Treponema vencentii (родственник Treponema denticola), Prevotella baroniae, Prevotella salivae и Prevotella spp. (родственники P. intermedia), а также Campylobacter concisus (родственник C. jejuni, возбудителя энтероколитов).
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