Copper-Containing Nanoparticles and Organic Complexes: Metal Reduction Triggers Rapid Cell Death via Oxidative Burst

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

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia

The efficacy of photodynamic therapy (PDT) strictly depends on the availability of molecular oxygen to trigger the light-induced generation of reactive species. Fluorocarbons have an increased ability to dissolve oxygen and are attractive tools for gas delivery. We synthesized three fluorous derivatives of chlorin with peripheral polyfluoroalkyl substituents. These compounds were used as precursors for preparing nanoemulsions with perfluorodecalin as an oxygen depot. Therefore, our formulations contained hydrophobic photosensitizers capable of absorbing monochromatic light in the long wavelength region and the oxygen carrier. These modifications did not alter the photosensitizing characteristics of chlorin such as the generation of singlet oxygen, the major cytocidal species in PDT. Emulsions readily entered HCT116 colon carcinoma cells and accumulated largely in mitochondria. Illumination of cells loaded with emulsions rapidly caused peroxidation of lipids and the loss of the plasma membrane integrity (photonecrosis). Most importantly, in PDT settings, emulsions potently sensitized cells cultured under prolonged (8 weeks) hypoxia as well as cells after oxygen depletion with sodium sulfite (acute hypoxia). The photodamaging potency of emulsions in hypoxia was significantly more pronounced compared to emulsion-free counterparts. Considering a negligible dark cytotoxicity, our materials emerge as efficient and biocompatible instruments for PDT-assisted eradication of hypoxic cells

Научные журналы по библиотековедению, библиографоведению и книговедению: история, реалии, перспективы

The article presents the presentations of the participants of the round table “Scientific Journals on Library Science, Bibliography Science and Book Studies: History, Realities, Prospects (to the 70th anniversary of the journal “Bibliotekovedenie” (Library Science)”, which took place on April 19, 2022 within the framework of the International Scientific and Practical Conference “Rumyantsev Readings — 2022”. The paper reflects the place and role of the professional scientific journals in the development of communications that contribute to the preservation of libraries as cultural heritage institutions and form the human capital and cultural potential of all generations of Russian citizens.The journal “Library Science”, established in 1952, became the nationwide scientific periodical of the library sector. Participants described in their speeches the characteristics of the publication activity of some Russian journals, professional periodicals of Belarus, Kazakhstan, Azerbaijan and the international scientific journal “Libri”. The authors highlighted the peculiarities of the creation of periodicals of the designated subject, their functioning, the management models used, the diversity of elements of publication policy and design: regional differences, typological characteristics of the founders, departmental affiliation, cultural traditions, the uniqueness of the historical conditions of creation, etc.The discussion resulted in unanimous recognition of the significant role of professional scientific periodicals in supporting the scientific infrastructure of libraries and providing methodological support of the sector, including research practices, as well as atmosphere of creativity and creative competencies. In the future, the journals are considered as points of growth of professional knowledge, interdisciplinary thinking and cultural communications, activators of the socio-cultural space.Представлены выступления участников круглого стола «Научные журналы по библиотековедению, библиографоведению и книговедению: история, реалии, перспективы (к 70-летию журнала “Библиотековедение”)», который состоялся 19 апреля 2022 г. в рамках Международной научно-практической конференции «Румянцевские чтения — 2022». Отражены место и роль профессиональных научных журналов в развитии коммуникаций, способствующих сохранению библиотек как учреждений культурного наследия и формирующих человеческий капитал и культурный потенциал всех поколений граждан России.Журнал «Библиотековедение», созданный в 1952 г., стал общенациональным научным периодическим изданием библиотечной отрасли, задачи которого в разные периоды фокусировались на проблемах становления библиотек как активных участников процессов, происходящих в обществе, и их отражении в научных исследованиях. «Библиотековедение» остается признанным и наиболее авторитетным журналом.В выступлениях участников были отмечены характеристики публикационной активности некоторых российских журналов, профессиональной периодики Беларуси, Казахстана, Азербайджана и международного научного журнала Libri.Выделены особенности создания периодических изданий обозначенной тематики, их функционирования, используемых управленческих моделей, разнообразие элементов публикационной политики и оформления: региональные различия, типологические характеристики учредителей, ведомственная принадлежность, культурные традиции, уникальность исторических условий создания и др.Итогом обсуждения стало единодушное признание значимой роли профессиональной научной периодики в поддержке научной инфраструктуры библиотек и методического обеспечения отрасли, включая исследовательские практики, атмосферу творчества и креативных компетенций. В перспективе журналы рассматриваются как точки роста профессиональных знаний, междисциплинарного мышления и культурных коммуникаций, активаторы социокультурного пространства