63 research outputs found

    Molecular modeling of drug delivery systems based on carbon nanostructures: structure, function, and potential applications for anticancer complexes of Pt(II)

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    The medication with Pt(II) drugs (cisplatin, carboplatin, and oxaliplatin) has been an effective alternative for treating cancers due to their notable inhibition of cancer cells growth and the prevention of metastasis. Nevertheless, the low selectivity of these metallodrugs for malignant cells produces severe side effects, which limit this chemotherapy. In this context, carbon nanohorns (CNHs) have been considered potential nanovectors for drugs, since they present low toxicity, drug-loading capacity, biodegradation routes, and biocompatibility when oxidized. However, there is still a lack of studies regarding the molecular behavior of these nanocarriers on cell membranes. The present work aims to characterize the interactions between inclusion complexes drug@CNH, which are formed by platinum drugs encapsulated in CNHs, and plasma membranes by using molecular dynamics simulations. The results demonstrated that the van der Waals contribution played a primary role (∼74%) for the complex stability, which explain the confined dynamics of drugs inside the CNHs. The free energy profiles revealed an endergonic character of the drug release processes from CNHs, in which the energy barrier for oxaliplatin release (~24 kcal mol–1 ) was ~30% larger than those for carboplatin and cisplatin (~18 kcal mol-1 ). The simulations also showed four stages of the interaction mechanism CNH--membrane: approach, insertion, permeation, and internalization. Despite the low structural disturbance of the membranes, the free energy barrier of ∼55 kcal mol-1 for the CNHs translocation indicated that this transport is kinetically unfavorable by passive process. The in silico experiments evidenced that the most likely mechanism of cisplatin delivery from CNHs involve the approach and insertion stages, where the nanovector adheres on the surface of cancer cells, as reported in in vitro studies. After this retention, the drug load may be slowly released in the tumor site. Finally, simulations of the cellular uptake of Pt(II) drugs also pointed out significant energy barriers (~30 kcal mol-1 ) for this process, which reflects their low permeability in membranes as discussed in experimental studies. In addition to reinforcing the potential of CNH as nanovector of Pt(II) drugs, the results presented in this thesis may assist and drive new experimental studies with CNHs, focusing on the development of less aggressive formulations for cancer treatments.A medicação com fármacos a base de Pt(II) (cisplatina, carboplatina e oxaliplatina) tem sido uma alternativa efetiva para tratar cânceres devido à sua notável inibição do crescimento de células cancerosas e a prevenção de metástases. No entanto, a baixa seletividade dessas metalodrogas por células cancerosas gera severos efeitos colaterais. Nesse contexto, nanohorns de carbono (CNHs) têm sido considerados potenciais nanovetores de fármacos, devido a baixa toxicidade, capacidade de carreamento de fármacos, rotas de biodegradação, e biocompatibilidade quando oxidados. Porém, existe uma carência de estudos tratando o comportamento desses nanocarreadores em biomembranas. Esse trabalho tem como objetivo caracterizar as interações entre complexos de inclusão fármaco@CNH, formados por fármacos de Pt(II) encapsulados em CNHs, e membranas usando simulações por dinâmica molecular. Os resultados demonstraram que a contribuição de van der Waals teve um papel primário (∼74%) na estabilidade dos complexos, o que explica a dinâmica confinada dos fármacos dentro dos CNHs. Os perfis de energia livre revelaram o caráter endergônico da liberação dos fármacos a partir de CNHs, nos quais a barreira de energia para a liberação da oxaliplatina (~24 kcal mol– 1 ) é ~30% maior do que aquelas para carboplatina e cisplatina. As simulações mostraram quatro estágios do mecanismo de interação CNH-membrana: aproximação, inserção, permeação e internalização. Apesar do baixo distúrbio estrutural das membranas, a barreira de energia livre de ∼55 kcal mol-1 para a translocação de CNHs indicou que esse transporte é desfavorável cineticamente via o processo passivo. Os experimentos in silico evidenciam que o mecanismo mais provável de entrega de cisplatina a partir de CNHs envolve a aproximação e inserção, onde o nanovetor adere na superfície de células cancerosas, como reportado em estudos in vitro. Após essa retenção, a carga de fármaco deve ser ligeiramente liberada no tumor. As simulações de captação celular de fármacos de Pt(II) também apontaram barreiras de energia significativas (∼30 kcal mol-1 ) para esse processo, o que reflete a baixa permeabilidade deles em membranas como discutido em estudos experimentais. Além de reforçar o potencial de CNHs como nanovetores de fármacos de Pt(II), os resultados apresentados nessa tese podem auxiliar e impulsionar novos estudos com CNHs, focando no desenvolvimento de formulações menos agressivas para tratamentos de câncer.FAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerai

    ATHENA Research Book, Volume 2

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    ATHENA European University is an association of nine higher education institutions with the mission of promoting excellence in research and innovation by enabling international cooperation. The acronym ATHENA stands for Association of Advanced Technologies in Higher Education. Partner institutions are from France, Germany, Greece, Italy, Lithuania, Portugal and Slovenia: University of Orléans, University of Siegen, Hellenic Mediterranean University, Niccolò Cusano University, Vilnius Gediminas Technical University, Polytechnic Institute of Porto and University of Maribor. In 2022, two institutions joined the alliance: the Maria Curie-Skłodowska University from Poland and the University of Vigo from Spain. Also in 2022, an institution from Austria joined the alliance as an associate member: Carinthia University of Applied Sciences. This research book presents a selection of the research activities of ATHENA University's partners. It contains an overview of the research activities of individual members, a selection of the most important bibliographic works of members, peer-reviewed student theses, a descriptive list of ATHENA lectures and reports from individual working sections of the ATHENA project. The ATHENA Research Book provides a platform that encourages collaborative and interdisciplinary research projects by advanced and early career researchers

    Chapter 34 - Biocompatibility of nanocellulose: Emerging biomedical applications

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    Nanocellulose already proved to be a highly relevant material for biomedical applications, ensued by its outstanding mechanical properties and, more importantly, its biocompatibility. Nevertheless, despite their previous intensive research, a notable number of emerging applications are still being developed. Interestingly, this drive is not solely based on the nanocellulose features, but also heavily dependent on sustainability. The three core nanocelluloses encompass cellulose nanocrystals (CNCs), cellulose nanofibrils (CNFs), and bacterial nanocellulose (BNC). All these different types of nanocellulose display highly interesting biomedical properties per se, after modification and when used in composite formulations. Novel applications that use nanocellulose includewell-known areas, namely, wound dressings, implants, indwelling medical devices, scaffolds, and novel printed scaffolds. Their cytotoxicity and biocompatibility using recent methodologies are thoroughly analyzed to reinforce their near future applicability. By analyzing the pristine core nanocellulose, none display cytotoxicity. However, CNF has the highest potential to fail long-term biocompatibility since it tends to trigger inflammation. On the other hand, neverdried BNC displays a remarkable biocompatibility. Despite this, all nanocelluloses clearly represent a flag bearer of future superior biomaterials, being elite materials in the urgent replacement of our petrochemical dependence

    Бутаковские чтения : материалы II Всероссийской с международным участием молодежной конференции, 13-15 декабря 2022 г., Томск

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    Сборник посвящён теоретическим и практическим проблемам цифровой энергетики и интеллектуальным энергетическим системам, теплофизическим спектрам энергетических технологий, производству тепловой и электрической энергии, экологическим проблемам энергетики, энергетическим системам и комплексам, энергосбережению и энергоэффективности, а также новациям инженерного образования. Представлен широкий круг исследований аспирантов, студентов и молодых учёных Томска и ряда других городов России

    The 2nd International Electronic Conference on Applied Sciences

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    This book is focused on the works presented at the 2nd International Electronic Conference on Applied Sciences, organized by Applied Sciences from 15 to 31 October 2021 on the MDPI Sciforum platform. Two decades have passed since the start of the 21st century. The development of sciences and technologies is growing ever faster today than in the previous century. The field of science is expanding, and the structure of science is becoming ever richer. Because of this expansion and fine structure growth, researchers may lose themselves in the deep forest of the ever-increasing frontiers and sub-fields being created. This international conference on the Applied Sciences was started to help scientists conduct their own research into the growth of these frontiers by breaking down barriers and connecting the many sub-fields to cut through this vast forest. These functions will allow researchers to see these frontiers and their surrounding (or quite distant) fields and sub-fields, and give them the opportunity to incubate and develop their knowledge even further with the aid of this multi-dimensional network

    Properties and Applications of Graphene and Its Derivatives

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    Graphene is a two-dimensional, one-atom-thick material made entirely of carbon atoms, arranged in a honeycomb lattice. Because of its distinctive mechanical (e.g., high strength and flexibility) and electronic (great electrical and thermal conductivities) properties, graphene is an ideal candidate in myriad applications. Thus, it has just begun to be engineered in electronics, photonics, biomedicine, and polymer-based composites, to name a few. The broad family of graphene nanomaterials (including graphene nanoplatelets, graphene oxide, graphene quantum dots, and many more) go beyond and aim higher than mere single-layer (‘pristine’) graphene, and thus, their potential has sparked the current Special Issue. In it, 18 contributions (comprising 14 research articles and 4 reviews) have portrayed probably the most interesting lines as regards future and tangible uses of graphene derivatives. Ultimately, understanding the properties of the graphene family of nanomaterials is crucial for developing advanced applications to solve important challenges in critical areas such as energy and health

    ICR ANNUAL REPORT 2022 (Volume 29)[All Pages]

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    This Annual Report covers from 1 January to 31 December 202

    Exploring the Multifaceted Roles of Glycosaminoglycans (GAGs) - New Advances and Further Challenges

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    Glycosaminoglycans are linear, anionic polysaccharides (GAGs) consisting of repeating disaccharides. GAGs are ubiquitously localized throughout the extracellular matrix (ECM) and to the cell membranes of cells in all tissues. They are either conjugated to protein cores in the form of proteoglycans, e.g., chondroitin/dermatan sulfate (CS/DS), heparin/heparan sulfate (Hep/HS) and keratan sulfate (KS), as well as non-sulfated hyaluronan (HA). By modulating biological signaling GAGs participate in the regulation of homeostasis and also participate in disease progression. The book, entitled “Exploring the multifaceted roles of glycosaminoglycans (GAGs)—new advances and further challenges”, features original research and review articles. These articles cover several GAG-related timely topics in structural biology and imaging; morphogenesis, cancer, and other disease therapy and drug developments; tissue engineering; and metabolic engineering. This book also includes an article illustrating how metabolic engineering can be used to create the novel chondroitin-like polysaccharide.A prerequisite for communicating in any discipline and across disciplines is familiarity with the appropriate terminology. Several nomenclature rules exist in the field of biochemistry. The historical description of GAGs follows IUPAC and IUB nomenclature. New structural depictions such as the structural nomenclature for glycan and their translation into machine-readable formats have opened the route for cross-references with popular bioinformatics resources and further connections with other exciting “omics” fields

    12th EASN International Conference on "Innovation in Aviation & Space for opening New Horizons"

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    Epoxy resins show a combination of thermal stability, good mechanical performance, and durability, which make these materials suitable for many applications in the Aerospace industry. Different types of curing agents can be utilized for curing epoxy systems. The use of aliphatic amines as curing agent is preferable over the toxic aromatic ones, though their incorporation increases the flammability of the resin. Recently, we have developed different hybrid strategies, where the sol-gel technique has been exploited in combination with two DOPO-based flame retardants and other synergists or the use of humic acid and ammonium polyphosphate to achieve non-dripping V-0 classification in UL 94 vertical flame spread tests, with low phosphorous loadings (e.g., 1-2 wt%). These strategies improved the flame retardancy of the epoxy matrix, without any detrimental impact on the mechanical and thermal properties of the composites. Finally, the formation of a hybrid silica-epoxy network accounted for the establishment of tailored interphases, due to a better dispersion of more polar additives in the hydrophobic resin
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