2024

Jump to: 2023, 2022

22 pages, 4552 KiB

Open AccessArticle

Inulin-Coated ZnO Nanoparticles: A Correlation between Preparation and Properties for Biostimulation Purposes

by Lorenzo Gontrani, Elvira Maria Bauer, Lorenzo Casoli, Cosimo Ricci, Angelo Lembo, Domenica Tommasa Donia, Simone Quaranta and Marilena Carbone

Int. J. Mol. Sci. 2024, 25(5), 2703; https://doi.org/10.3390/ijms25052703 - 26 Feb 2024

Cited by 1 | Viewed by 749

Abstract

Within the framework of plant biostimulation, a pivotal role is played by the achievement of low-cost, easily prepared nanoparticles for priming purposes. Therefore, in this report, two different synthetic strategies are described to engineer zinc oxide nanoparticles with an inulin coating. In both [...] Read more.

Within the framework of plant biostimulation, a pivotal role is played by the achievement of low-cost, easily prepared nanoparticles for priming purposes. Therefore, in this report, two different synthetic strategies are described to engineer zinc oxide nanoparticles with an inulin coating. In both protocols, i.e., two-step and gel-like one-pot protocols, nanoparticles with a highly pure ZnO kernel are obtained when the reaction is carried out at T ≥ 40 °C, as ascertained by XRD and ATR/FTIR studies. However, a uniformly dispersed, highly homogeneous coating is achieved primarily when different temperatures, i.e., 60 °C and 40 °C, are employed in the two phases of the step-wise synthesis. In addition, a different binding mechanism, i.e., complexation, occurs in this case. When the gel-like process is employed, a high degree of coverage by the fructan is attained, leading to micrometric coated aggregates of nanometric particles, as revealed by SEM investigations. All NPs from the two-step synthesis feature electronic bandgaps in the 3.25–3.30 eV range in line with previous studies, whereas the extensive coating causes a remarkable 0.4 eV decrease in the bandgap. Overall, the global analysis of the investigations indicates that the samples synthesized at 60 °C and 40 °C are the best suited for biostimulation. Proof-of-principle assays upon Vicia faba seed priming with Zn5 and Zn5@inu indicated an effective growth stimulation of seedlings at doses of 100 mgKg⁻¹, with concomitant Zn accumulation in the leaves. Full article

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30 pages, 1622 KiB

Open AccessReview

Targeted Radium Alpha Therapy in the Era of Nanomedicine: In Vivo Results

by György Trencsényi, Csaba Csikos and Zita Képes

Int. J. Mol. Sci. 2024, 25(1), 664; https://doi.org/10.3390/ijms25010664 - 04 Jan 2024

Viewed by 1986

Abstract

Targeted alpha-particle therapy using radionuclides with alpha emission is a rapidly developing area in modern cancer treatment. To selectively deliver alpha-emitting isotopes to tumors, targeting vectors, including monoclonal antibodies, peptides, small molecule inhibitors, or other biomolecules, are attached to them, which ensures specific [...] Read more.

Targeted alpha-particle therapy using radionuclides with alpha emission is a rapidly developing area in modern cancer treatment. To selectively deliver alpha-emitting isotopes to tumors, targeting vectors, including monoclonal antibodies, peptides, small molecule inhibitors, or other biomolecules, are attached to them, which ensures specific binding to tumor-related antigens and cell surface receptors. Although earlier studies have already demonstrated the anti-tumor potential of alpha-emitting radium (Ra) isotopes—Radium-223 and Radium-224 (^223/224Ra)—in the treatment of skeletal metastases, their inability to complex with target-specific moieties hindered application beyond bone targeting. To exploit the therapeutic gains of Ra across a wider spectrum of cancers, nanoparticles have recently been embraced as carriers to ensure the linkage of ^223/224Ra to target-affine vectors. Exemplified by prior findings, Ra was successfully bound to several nano/microparticles, including lanthanum phosphate, nanozeolites, barium sulfate, hydroxyapatite, calcium carbonate, gypsum, celestine, or liposomes. Despite the lengthened tumor retention and the related improvement in the radiotherapeutic effect of ^223/224Ra coupled to nanoparticles, the in vivo assessment of the radiolabeled nanoprobes is a prerequisite prior to clinical usage. For this purpose, experimental xenotransplant models of different cancers provide a well-suited scenario. Herein, we summarize the latest achievements with ^223/224Ra-doped nanoparticles and related advances in targeted alpha radiotherapy. Full article

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2023

Jump to: 2024, 2022

29 pages, 4508 KiB

Open AccessReview

Recent Advances in Biomimetic Nanocarrier-Based Photothermal Therapy for Cancer Treatment

by Juan Gallo and Aranzazu Villasante

Int. J. Mol. Sci. 2023, 24(20), 15484; https://doi.org/10.3390/ijms242015484 - 23 Oct 2023

Cited by 1 | Viewed by 1448

Abstract

Nanomedicine presents innovative solutions for cancer treatment, including photothermal therapy (PTT). PTT centers on the design of photoactivatable nanoparticles capable of absorbing non-toxic near-infrared light, generating heat within target cells to induce cell death. The successful transition from benchside to bedside application of [...] Read more.

Nanomedicine presents innovative solutions for cancer treatment, including photothermal therapy (PTT). PTT centers on the design of photoactivatable nanoparticles capable of absorbing non-toxic near-infrared light, generating heat within target cells to induce cell death. The successful transition from benchside to bedside application of PTT critically depends on the core properties of nanoparticles responsible for converting light into heat and the surface properties for precise cell-specific targeting. Precisely targeting the intended cells remains a primary challenge in PTT. In recent years, a groundbreaking approach has emerged to address this challenge by functionalizing nanocarriers and enhancing cell targeting. This strategy involves the creation of biomimetic nanoparticles that combine desired biocompatibility properties with the immune evasion mechanisms of natural materials. This review comprehensively outlines various strategies for designing biomimetic photoactivatable nanocarriers for PTT, with a primary focus on its application in cancer therapy. Additionally, we shed light on the hurdles involved in translating PTT from research to clinical practice, along with an overview of current clinical applications. Full article

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16 pages, 6908 KiB

Open AccessArticle

Iron Oxide Nanoparticles with Supramolecular Ureido-Pyrimidinone Coating for Antimicrobial Peptide Delivery

by Chiara Turrina, Jennifer Cookman, Riccardo Bellan, Jiankang Song, Margret Paar, Patricia Y. W. Dankers, Sonja Berensmeier and Sebastian P. Schwaminger

Int. J. Mol. Sci. 2023, 24(19), 14649; https://doi.org/10.3390/ijms241914649 - 27 Sep 2023

Viewed by 1447

Abstract

Antimicrobial peptides (AMPs) can kill bacteria by disrupting their cytoplasmic membrane, which reduces the tendency of antibacterial resistance compared to conventional antibiotics. Their possible toxicity to human cells, however, limits their applicability. The combination of magnetically controlled drug delivery and supramolecular engineering can [...] Read more.

Antimicrobial peptides (AMPs) can kill bacteria by disrupting their cytoplasmic membrane, which reduces the tendency of antibacterial resistance compared to conventional antibiotics. Their possible toxicity to human cells, however, limits their applicability. The combination of magnetically controlled drug delivery and supramolecular engineering can help to reduce the dosage of AMPs, control the delivery, and improve their cytocompatibility. Lasioglossin III (LL) is a natural AMP form bee venom that is highly antimicrobial. Here, superparamagnetic iron oxide nanoparticles (IONs) with a supramolecular ureido-pyrimidinone (UPy) coating were investigated as a drug carrier for LL for a controlled delivery to a specific target. Binding to IONs can improve the antimicrobial activity of the peptide. Different transmission electron microscopy (TEM) techniques showed that the particles have a crystalline iron oxide core with a UPy shell and UPy fibers. Cytocompatibility and internalization experiments were carried out with two different cell types, phagocytic and nonphagocytic cells. The drug carrier system showed good cytocompatibility (>70%) with human kidney cells (HK-2) and concentration-dependent toxicity to macrophagic cells (THP-1). The particles were internalized by both cell types, giving them the potential for effective delivery of AMPs into mammalian cells. By self-assembly, the UPy-coated nanoparticles can bind UPy-functionalized LL (UPy-LL) highly efficiently (99%), leading to a drug loading of 0.68 g g⁻¹. The binding of UPy-LL on the supramolecular nanoparticle system increased its antimicrobial activity against E. coli (MIC 3.53 µM to 1.77 µM) and improved its cytocompatible dosage for HK-2 cells from 5.40 µM to 10.6 µM. The system showed higher cytotoxicity (5.4 µM) to the macrophages. The high drug loading, efficient binding, enhanced antimicrobial behavior, and reduced cytotoxicity makes ION@UPy-NH₂ an interesting drug carrier for AMPs. The combination with superparamagnetic IONs allows potential magnetically controlled drug delivery and reduced drug amount of the system to address intracellular infections or improve cancer treatment. Full article

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18 pages, 3332 KiB

Open AccessArticle

Extracellular Vesicles Isolation from Large Volume Samples Using a Polydimethylsiloxane-Free Microfluidic Device

by Cristina Bajo-Santos, Miks Priedols, Pauls Kaukis, Gunita Paidere, Romualds Gerulis-Bergmanis, Gatis Mozolevskis, Arturs Abols and Roberts Rimsa

Int. J. Mol. Sci. 2023, 24(9), 7971; https://doi.org/10.3390/ijms24097971 - 27 Apr 2023

Cited by 2 | Viewed by 1922

Abstract

Extracellular vesicles (EV) have many attributes important for biomedicine; however, current EV isolation methods require long multi-step protocols that generally involve bulky equipment that cannot be easily translated to clinics. Our aim was to design a new cyclic olefin copolymer–off-stoichiometry thiol-ene (COC–OSTE) asymmetric [...] Read more.

Extracellular vesicles (EV) have many attributes important for biomedicine; however, current EV isolation methods require long multi-step protocols that generally involve bulky equipment that cannot be easily translated to clinics. Our aim was to design a new cyclic olefin copolymer–off-stoichiometry thiol-ene (COC–OSTE) asymmetric flow field fractionation microfluidic device that could isolate EV from high-volume samples in a simple and efficient manner. We tested the device with large volumes of urine and conditioned cell media samples, and compared it with the two most commonly used EV isolation methods. Our device was able to separate particles by size and buoyancy, and the attained size distribution was significantly smaller than other methods. This would allow for targeting EV size fractions of interest in the future. However, the results were sample dependent, with some samples showing significant improvement over the current EV separation methods. We present a novel design for a COC–OSTE microfluidic device, based on bifurcating asymmetric flow field-flow fractionation (A4F) technology, which is able to isolate EV from large volume samples in a simple, continuous-flow manner. Its potential to be mass-manufactured increases the chances of implementing EV isolation in a clinical or industry-friendly setting, which requires high repeatability and throughput. Full article

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23 pages, 10927 KiB

Open AccessArticle

Bioinspired Synthesis of Magnetic Nanoparticles Based on Iron Oxides Using Orange Waste and Their Application as Photo-Activated Antibacterial Agents

by David Giancarlo García, Cristina Garzón-Romero, Mateo Alejandro Salazar, Karina J. Lagos, Kleber Orlando Campaña, Alexis Debut, Karla Vizuete, Miryan Rosita Rivera, Dario Niebieskikwiat, Maria J. Benitez and María Paulina Romero

Int. J. Mol. Sci. 2023, 24(5), 4770; https://doi.org/10.3390/ijms24054770 - 01 Mar 2023

Cited by 4 | Viewed by 2764

Abstract

Magnetic nanoparticles based on iron oxides (MNPs-Fe) have been proposed as photothermal agents (PTAs) within antibacterial photothermal therapy (PTT), aiming to counteract the vast health problem of multidrug-resistant bacterial infections. We present a quick and easy green synthesis (GS) to prepare MNPs-Fe harnessing [...] Read more.

Magnetic nanoparticles based on iron oxides (MNPs-Fe) have been proposed as photothermal agents (PTAs) within antibacterial photothermal therapy (PTT), aiming to counteract the vast health problem of multidrug-resistant bacterial infections. We present a quick and easy green synthesis (GS) to prepare MNPs-Fe harnessing waste. Orange peel extract (organic compounds) was used as a reducing, capping, and stabilizing agent in the GS, which employed microwave (MW) irradiation to reduce the synthesis time. The produced weight, physical–chemical features and magnetic features of the MNPs-Fe were studied. Moreover, their cytotoxicity was assessed in animal cell line ATCC RAW 264.7, as well as their antibacterial activity against Staphylococcus aureus and Escherichia coli. We found that the 50GS-MNPs-Fe sample (prepared by GS, with 50% v/v of NH₄OH and 50% v/v of orange peel extract) had an excellent mass yield. Its particle size was ~50 nm with the presence of an organic coating (terpenes or aldehydes). We believe that this coating improved the cell viability in extended periods (8 days) of cell culture with concentrations lower than 250 µg·mL⁻¹, with respect to the MNPs-Fe obtained by CO and single MW, but it did not influence the antibacterial effect. The bacteria inhibition was attributed to the plasmonic of 50GS-MNPs-Fe (photothermal effect) by irradiation with red light (630 nm, 65.5 mW·cm⁻², 30 min). We highlight the superparamagnetism of the 50GS-MNPs-Fe over 60 K in a broader temperature range than the MNPs-Fe obtained by CO (160.09 K) and MW (211.1 K). Therefore, 50GS-MNPs-Fe could be excellent candidates as broad-spectrum PTAs in antibacterial PTT. Furthermore, they might be employed in magnetic hyperthermia, magnetic resonance imaging, oncological treatments, and so on. Full article

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18 pages, 1861 KiB

Open AccessReview

Application Progress of the Single Domain Antibody in Medicine

by Huaping Tang, Yuan Gao and Jiangyuan Han

Int. J. Mol. Sci. 2023, 24(4), 4176; https://doi.org/10.3390/ijms24044176 - 20 Feb 2023

Cited by 6 | Viewed by 4301

Abstract

The camelid-derived single chain antibody (sdAb), also termed VHH or nanobody, is a unique, functional heavy (H)-chain antibody (HCAb). In contrast to conventional antibodies, sdAb is a unique antibody fragment consisting of a heavy-chain variable domain. It lacks light chains and a first [...] Read more.

The camelid-derived single chain antibody (sdAb), also termed VHH or nanobody, is a unique, functional heavy (H)-chain antibody (HCAb). In contrast to conventional antibodies, sdAb is a unique antibody fragment consisting of a heavy-chain variable domain. It lacks light chains and a first constant domain (CH1). With a small molecular weight of only 12~15 kDa, sdAb has a similar antigen-binding affinity to conventional Abs but a higher solubility, which exerts unique advantages for the recognition and binding of functional, versatile, target-specific antigen fragments. In recent decades, with their unique structural and functional features, nanobodies have been considered promising agents and alternatives to traditional monoclonal antibodies. As a new generation of nano-biological tools, natural and synthetic nanobodies have been used in many fields of biomedicine, including biomolecular materials, biological research, medical diagnosis and immune therapies. This article briefly overviews the biomolecular structure, biochemical properties, immune acquisition and phage library construction of nanobodies and comprehensively reviews their applications in medical research. It is expected that this review will provide a reference for the further exploration and unveiling of nanobody properties and function, as well as a bright future for the development of drugs and therapeutic methods based on nanobodies. Full article

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13 pages, 2627 KiB

Open AccessArticle

Aggregation and Gelation Behavior of Stereocomplexed Four-Arm PLA-PEG Copolymers Containing Neutral or Cationic Linkers

by Francesca Signori, Jos W. H. Wennink, Simona Bronco, Jan Feijen, Marcel Karperien, Ranieri Bizzarri and Pieter J. Dijkstra

Int. J. Mol. Sci. 2023, 24(4), 3327; https://doi.org/10.3390/ijms24043327 - 07 Feb 2023

Cited by 1 | Viewed by 1150

Abstract

Poly(lactide) (PLA) and poly(ethylene glycol) (PEG)-based hydrogels were prepared by mixing phosphate buffer saline (PBS, pH 7.4) solutions of four-arm (PEG-PLA)₂-R-(PLA-PEG)₂ enantiomerically pure copolymers having the opposite chirality of the poly(lactide) blocks. Dynamic Light Scattering, rheology measurements, and fluorescence spectroscopy [...] Read more.

Poly(lactide) (PLA) and poly(ethylene glycol) (PEG)-based hydrogels were prepared by mixing phosphate buffer saline (PBS, pH 7.4) solutions of four-arm (PEG-PLA)₂-R-(PLA-PEG)₂ enantiomerically pure copolymers having the opposite chirality of the poly(lactide) blocks. Dynamic Light Scattering, rheology measurements, and fluorescence spectroscopy suggested that, depending on the nature of the linker R, the gelation process followed rather different mechanisms. In all cases, mixing of equimolar amounts of the enantiomeric copolymers led to micellar aggregates with a stereocomplexed PLA core and a hydrophilic PEG corona. Yet, when R was an aliphatic heptamethylene unit, temperature-dependent reversible gelation was mainly induced by entanglements of PEG chains at concentrations higher than 5 wt.%. When R was a linker containing cationic amine groups, thermo-irreversible hydrogels were promptly generated at concentrations higher than 20 wt.%. In the latter case, stereocomplexation of the PLA blocks randomly distributed in micellar aggregates is proposed as the major determinant of the gelation process. Full article

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40 pages, 8883 KiB

Open AccessConference Report

Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change

by Jekaterina Erenpreisa, Alessandro Giuliani, Kenichi Yoshikawa, Martin Falk, Georg Hildenbrand, Kristine Salmina, Talivaldis Freivalds, Ninel Vainshelbaum, Jonas Weidner, Aaron Sievers, Götz Pilarczyk and Michael Hausmann

Int. J. Mol. Sci. 2023, 24(3), 2658; https://doi.org/10.3390/ijms24032658 - 31 Jan 2023

Cited by 6 | Viewed by 2614

Abstract

Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing [...] Read more.

Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different parts of the genome. Most research so far has shed light on the puzzle pieces at these levels. This article, however, attempts an integrative approach to genome expression regulation incorporating these different layers. Under environmental stress or during cell development, differentiation towards specialized cell types, or to dysfunctional tumor, the cell nucleus seems to react as a whole through coordinated changes at all levels of control. This implies the need for a framework in which biological, chemical, and physical manifestations can serve as a basis for a coherent theory of gene self-organization. An international symposium held at the Biomedical Research and Study Center in Riga, Latvia, on 25 July 2022 addressed novel aspects of the abovementioned topic. The present article reviews the most recent results and conclusions of the state-of-the-art research in this multidisciplinary field of science, which were delivered and discussed by scholars at the Riga symposium. Full article

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31 pages, 7583 KiB

Open AccessArticle

Zein Nanoparticles Containing Arginine-Based Surfactants: Physicochemical Characterization and Effect on the Biological Properties

by Lourdes Pérez, Adrià Sentís, Zakaria Hafidi, Aurora Pinazo, Maria Teresa García, Manuel Martín-Pastor and Francisco Fábio Oliveira de Sousa

Int. J. Mol. Sci. 2023, 24(3), 2568; https://doi.org/10.3390/ijms24032568 - 29 Jan 2023

Cited by 2 | Viewed by 1837

Abstract

Cationic surfactants carry antimicrobial activity, based on their interaction and disruption of cell membranes. Nonetheless, their intrinsic toxicity limits their applicability. To overcome this issue, a feasible strategy consists of using solid nanoparticles to improve their delivery. The zein nanoparticles were loaded with [...] Read more.

Cationic surfactants carry antimicrobial activity, based on their interaction and disruption of cell membranes. Nonetheless, their intrinsic toxicity limits their applicability. To overcome this issue, a feasible strategy consists of using solid nanoparticles to improve their delivery. The zein nanoparticles were loaded with four cationic arginine-based surfactants: one single chain Nα-lauroyl-arginine (LAM) and three Gemini surfactants Nα Nω-Bis (Nα-lauroyl-arginine) α, ω—diamide) (C₃(LA)₂, C₆(LA)₂ and C₉(LA)₂). Blank and loaded zein nanoparticles were characterized in terms of size, polydispersity and zeta potential. Furthermore, the antimicrobial activity against bacteria and yeasts and the hemolytic activity were investigated and compared to the surfactants in a solution. Nanoparticles were found to be monodisperse, presenting a size of between 180–341 nm, a pdI of <0.2 and a positive zeta potential of between +13 and +53 mV, remaining stable over 365 days. The nanoencapsulation maintained the antimicrobial activity as unaltered, while the extensive hemolytic activity found for the surfactants in a solution was reduced drastically. Nuclear Magnetic Ressonance (NMR), molecular docking and monolayer findings indicated that zein entraps the surfactants, interfering in the surfactant–membrane interactions. Accordingly, the nanoepcasulation of arginine surfactants improved their selectivity, while the cationic charges were free to attack and destroy bacteria and fungi; the aliphatic chains were not available to disrupt the cellular membranes. Full article

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25 pages, 3426 KiB

Open AccessArticle

Folic-Acid-Conjugated Thermoresponsive Polymeric Particles for Targeted Delivery of 5-Fluorouracil to CRC Cells

by Sylwia Milewska, Gabriela Siemiaszko, Agnieszka Zofia Wilczewska, Iwona Misztalewska-Turkowicz, Karolina Halina Markiewicz, Dawid Szymczuk, Diana Sawicka, Halina Car, Ryszard Lazny and Katarzyna Niemirowicz-Laskowska

Int. J. Mol. Sci. 2023, 24(2), 1364; https://doi.org/10.3390/ijms24021364 - 10 Jan 2023

Cited by 4 | Viewed by 1862

Abstract

Colorectal cancer is the fourth most common cancer worldwide and the third most frequently diagnosed form of cancer associated with high mortality rates. Recently, targeted drug delivery systems have been under increasing attention owing to advantages such as high therapeutic effectiveness with a [...] Read more.

Colorectal cancer is the fourth most common cancer worldwide and the third most frequently diagnosed form of cancer associated with high mortality rates. Recently, targeted drug delivery systems have been under increasing attention owing to advantages such as high therapeutic effectiveness with a significant depletion in adverse events. In this report, we describe the biocompatible and thermoresponsive FA-conjugated PHEA-b-PNIPAAm copolymers as nanocarriers for the delivery of 5-FU. The block copolymers were obtained using RAFT (Reversible Addition–Fragmentation chain Transfer) polymerization and were characterized by methods such as SEC (Size Exclusion Chromatography), NMR (Nuclear Magnetic Resonance), UV–Vis (Ultraviolet–Visible), FT-IR (Fourier Transform Infrared) spectroscopy, and TGA (Thermogravimetric Analysis). Nanoparticles were formed from polymers with and without the drug-5-fluorouracil, which was confirmed using DLS (Dynamic Light Scattering), zeta potential measurements, and TEM (Transmission Electron Microscopy) imaging. The cloud points of the polymers were found to be close to the temperature of the human body. Eventually, polymeric carriers were tested as drug delivery systems for the safety, compatibility, and targeting of colorectal cancer cells (CRC). The biological evaluation indicated high compatibility with the representative host cells. Furthermore, it showed that proposed nanosystems might have therapeutic potential as mitigators for 5-FU-induced monocytopenia, cardiotoxicity, and other chemotherapy-associated disorders. Moreover, results show increased cytotoxicity against cancer cells compared to the drug, including a line with a drug resistance phenotype. Additionally, the ability of synthesized carriers to induce apoptosis and necrosis in treated CRC cells has been confirmed. Undoubtedly, the presented aspects of colorectal cancer therapy promise future solutions to overcome the conventional limitations of current treatment regimens for this type of cancer and to improve the quality of life of the patients. Full article

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18 pages, 3724 KiB

Open AccessArticle

Effects of Magnetic Nanoparticles on the Functional Activity of Human Monocytes and Dendritic Cells

by Marta Donini, Francesca Pettinella, Giorgia Zanella, Salvatore Calogero Gaglio, Carlo Laudanna, Monica Jimenez-Carretero, Concepcion Jimenez-Lopez, Massimiliano Perduca and Stefano Dusi

Int. J. Mol. Sci. 2023, 24(2), 1358; https://doi.org/10.3390/ijms24021358 - 10 Jan 2023

Cited by 3 | Viewed by 2091

Abstract

The use of nanoparticles in medicine is sometimes hampered by their potential to activate immune cells, eliciting inflammation or allergy. We investigated whether magnetic nanoparticles (MNPs) or biomimetic magnetic nanoparticles (BMNPs) affect relevant activities of human monocytes. We found that the nanoparticles neither [...] Read more.

The use of nanoparticles in medicine is sometimes hampered by their potential to activate immune cells, eliciting inflammation or allergy. We investigated whether magnetic nanoparticles (MNPs) or biomimetic magnetic nanoparticles (BMNPs) affect relevant activities of human monocytes. We found that the nanoparticles neither elicited the production of pro-inflammatory mediators IL-6 and TNFα by resting monocytes (when BMNP dose < 300 μg/mL) nor enhanced their secretion induced by R848, a molecule engaging virus-recognizing receptors, or bacterial lipopolysaccharide (LPS). MNPs and BMNPs neither induced the generation of reactive oxygen species (ROS), nor affected the ROS production elicited by the NADPH oxidase activator phorbol myristate acetate (PMA) or the fungal derivative β-glucan. BMNPs, but not MNPs, caused an up-regulation of the maturation markers CD80, CD83, and CD86 in immature monocyte-derived dendritic cells (DCs), whereas both nanoparticles did not affect the LPS-induced expression of these markers. Moreover, the nanoparticles were greedily ingested by monocytes and DCs without altering their viability. Therefore, these nanoparticles are candidates for medical applications because they do not activate pro-inflammatory activities of monocytes. Furthermore, their ability to stimulate DC maturation could be used for the design of vaccines. Moreover, harmlessly engulfed nanoparticles could be vehicles to carry molecules inside the immune cells to regulate the immune response. Full article

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2022

Jump to: 2024, 2023

16 pages, 3369 KiB

Open AccessArticle

Efficient and Reusable Sorbents Based on Nanostructured BN Coatings for Water Treatment from Antibiotics

by Kristina Yu. Kotyakova, Liubov Yu. Antipina, Pavel B. Sorokin and Dmitry V. Shtansky

Int. J. Mol. Sci. 2022, 23(24), 16097; https://doi.org/10.3390/ijms232416097 - 17 Dec 2022

Cited by 1 | Viewed by 1768

Abstract

Increasing contamination of wastewater with antibiotics used in agriculture, animal husbandry, and medicine is a serious problem for all living things. To address this important issue, we have developed an efficient platform based on a high specific surface area hexagonal boron nitride (BN) [...] Read more.

Increasing contamination of wastewater with antibiotics used in agriculture, animal husbandry, and medicine is a serious problem for all living things. To address this important issue, we have developed an efficient platform based on a high specific surface area hexagonal boron nitride (BN) coating formed by numerous nanopetals and nanoneedles. The maximum sorption capacity of 1 × 1 cm² BN coatings is 502.78 µg/g (tetracycline, TET), 315.75 µg/g (ciprofloxacin, CIP), 400.17 µg/g (amoxicillin, AMOX), and 269.7 µg/g (amphotericin B, AMP), which exceeds the sorption capacity of many known materials. Unlike nanoparticles, BN-coated Si wafers are easy to place in and remove from antibiotic-contaminated aqueous solutions, and are easy to clean. When reusing the adsorbents, 100% efficiency was observed at the same time intervals as in the first cleaning cycle: 7 days (TET) and 14 days (CIP, AMOX, AMP) at 10 µg/mL, 14 days (TET, CIP, and AMOX) and 28 days (AMP) at 50 µg/mL, and 14 days (TET) and 28 days (CIP, AMOX and AMP) at 100 µg/mL. The results obtained showed that TET and CIP are best adsorbed on the surface of BN, so TET was chosen as an example for further theoretical modeling of the sorption process. It was found that adsorption is the main mechanism, and this process is spontaneous and endothermic. This highlights the importance of a high specific surface area for the efficient removal of antibiotics from aqueous solutions. Full article

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24 pages, 10206 KiB

Open AccessArticle

The Impact of the Azo-Chromophore Sort on the Features of the Supramolecular Azopolyimide Films Desired to Be Used as Substrates for Flexible Electronics

by Iuliana Stoica, Elena-Luiza Epure, Andreea Irina Barzic, Ilarion Mihaila, Catalin-Paul Constantin and Ion Sava

Int. J. Mol. Sci. 2022, 23(23), 15223; https://doi.org/10.3390/ijms232315223 - 03 Dec 2022

Cited by 3 | Viewed by 1309

Abstract

High-performance supramolecular polyimide systems were synthesized via a simple and innovative approach using two types of azo-chromophores, leading to concomitant special properties: high thermostability, the ability to be processed in the form of films with high flexibility, adequate morphological features, and good structuring [...] Read more.

High-performance supramolecular polyimide systems were synthesized via a simple and innovative approach using two types of azo-chromophores, leading to concomitant special properties: high thermostability, the ability to be processed in the form of films with high flexibility, adequate morphological features, and good structuring capacity via phase mask ultraviolet (UV) laser irradiation, induced by the presence of the azo groups (–N=N–). The dimension and the anisotropy degree of the micro/nano patterns obtained on the surface of the flexible films (determined by atomic force microscopy) depend on the azo-dye type used in the supramolecular azopolyimide synthesis, which were higher when the azo-chromophore containing a –cyano group (–C≡N) was used. The molecular dynamics method, an excellent tool for an in-depth examination of the intermolecular interactions, was used to explain the morphological aspects. Energetic, dynamic and structural parameters were calculated for the two systems containing azo-chromophores, as well as for the pristine polymer system. It was highlighted that the van der Waals forces make a major contribution to the intermolecular interactions. The results from the combination of the dynamic analysis and the concentration profile explain the better mobility of the polyimide chains with a maximum content of azo groups in the cis configuration compared to the other systems. Taking all these data into account, the surfaces of the films can be tuned as required for the proposed applications, namely as substrates for flexible electronis. Full article

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15 pages, 3416 KiB

Open AccessArticle

One Step before Synthesis: Structure–Property–Condition Relationship Models to Sustainable Design of Efficient TiO₂-Based Multicomponent Nanomaterials

by Alicja Mikolajczyk and Dawid Falkowski

Int. J. Mol. Sci. 2022, 23(21), 13196; https://doi.org/10.3390/ijms232113196 - 30 Oct 2022

Viewed by 1210

Abstract

To control the photocatalytic activity, it is essential to consider several parameters affecting the structure of ordered multicomponent TiO₂-based photocatalytic nanotubes. The lack of systematic knowledge about the relationship between structure, property, and preparation parameters may be provided by applying a [...] Read more.

To control the photocatalytic activity, it is essential to consider several parameters affecting the structure of ordered multicomponent TiO₂-based photocatalytic nanotubes. The lack of systematic knowledge about the relationship between structure, property, and preparation parameters may be provided by applying a machine learning (ML) methodology and predictive models based on the quantitative structure-property-condition relationship (QSPCR). In the present study, for the first time, the quantitative mapping of preparation parameters, morphology, and photocatalytic activity of 136 TiO₂ NTs doped with metal and non-metal nanoparticles synthesized with the one-step anodization method has been investigated via linear and nonlinear ML methods. Moreover, the developed QSPCR model, for the first time, provides systematic knowledge supporting the design of effective TiO₂-based nanotubes by proper structure manipulation. The proposed computer-aided methodology reduces cost and speeds up the process (optimize) of efficient photocatalysts’ design at the earliest possible stage (before synthesis) in line with the sustainability-by-design strategy. Full article

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14 pages, 5934 KiB

Open AccessArticle

Photocatalytic Activity of TiO₂ Coatings Obtained at Room Temperature on a Polymethyl Methacrylate Substrate

by Mairis Iesalnieks, Raivis Eglītis, Tālis Juhna, Krišjānis Šmits and Andris Šutka

Int. J. Mol. Sci. 2022, 23(21), 12936; https://doi.org/10.3390/ijms232112936 - 26 Oct 2022

Cited by 5 | Viewed by 2060

Abstract

Titanium dioxide (TiO₂) coatings have a wide range of applications. Anatase exhibits hydrophilic, antimicrobial, and photocatalytic properties for the degradation of organic pollutants or water splitting. The main challenge is to obtain durable anatase nanoparticle coatings on plastic substrates by using [...] Read more.

Titanium dioxide (TiO₂) coatings have a wide range of applications. Anatase exhibits hydrophilic, antimicrobial, and photocatalytic properties for the degradation of organic pollutants or water splitting. The main challenge is to obtain durable anatase nanoparticle coatings on plastic substrates by using straightforward approaches. In the present study, we revealed the preparation of a transparent TiO₂ coating on polymethylmethacrylate (PMMA), widely used for organic optical fibres as well as other polymer substrates such as polypropylene (PP), polystyrene (PS), and polycarbonate (PC). The films were spin-coated at room temperature without annealing; therefore, our approach can be used for thermo-sensitive substrates. The deposition was successful due to the use of stripped ultra-small (<4 nm) TiO₂ particles. Coatings were studied for the photocatalytic degradation of organic pollutants such as MB, methyl orange (MO), and rhodamine B (RB) under UV light. The TiO₂ coating on PMMA degraded over 80% of RB in 300 min under a 365 nm, 100 W mercury lamp, showing a degradation rate constant of 6 × 10⁻³ min⁻¹. The coatings were stable and showed no significant decrease in degradation activity even after five cycles. Full article

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18 pages, 4170 KiB

Open AccessArticle

Boosted Activity of g-C₃N₄/UiO-66-NH₂ Heterostructures for the Photocatalytic Degradation of Contaminants in Water

by Rafael R. Solís, María Alejandra Quintana, María Ángeles Martín-Lara, Antonio Pérez, Mónica Calero and Mario J. Muñoz-Batista

Int. J. Mol. Sci. 2022, 23(21), 12871; https://doi.org/10.3390/ijms232112871 - 25 Oct 2022

Cited by 10 | Viewed by 2161

Abstract

The combination of graphitic carbon nitride and the metal-organic framework UiO-66-NH₂ has been developed with the aim to enhance the photocatalytic activity of pure semiconductors. Different proportions of g-C₃N₄ and UiO-66-NH₂ were combined. Complete characterization analysis of the [...] Read more.

The combination of graphitic carbon nitride and the metal-organic framework UiO-66-NH₂ has been developed with the aim to enhance the photocatalytic activity of pure semiconductors. Different proportions of g-C₃N₄ and UiO-66-NH₂ were combined. Complete characterization analysis of the resulting photocatalytic materials was conducted, including N₂ adsorption isotherms, XRD, FTIR, STEM-EDX microscopy, DRS-UV-visible, and photoluminescence. The photocatalytic activity was tested in an aqueous solution for the removal of acetaminophen as the target pollutant. From the obtained results, less than 50% of UiO-66-NH₂ incorporated in the g-C₃N₄ structure enhanced the photocatalytic degradation rate of both bare semiconductors. Concretely, 75% of g-C₃N₄ in the final g-C₃N₄/UiO-66-NH₂ heterostructure led to the best results, i.e., complete acetaminophen elimination initially at 5 mg·L⁻¹ in 2 h with a pseudo-first order rate constant of ca. 2 h⁻¹. The presence of UiO-66-NH₂ in the g-C₃N₄ enhanced the optoelectronic properties, concretely, the separation of the photo-generated charges was improved according to photoluminescence characterization. The better photo-absorption uptake was also confirmed by the determination of the quantum efficiency values of the heterostructure if compared to either pure g-C₃N₄ or UiO-66-NH₂. This photocatalyst with the best activity was further tested at different pH values, with the best degradation rate at a pH close to the pH_pzc ~4.15 of the solid. Sequential recycling tests demonstrated that the heterostructure was stable after five cycles of use, i.e., 15 h. A high contribution of photo-generated holes in the process of the degradation of acetaminophen, followed marginally by superoxide radicals, was suggested by scavenger tests. Full article

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12 pages, 2057 KiB

Open AccessArticle

Influence of Different Salts on the G-Quadruplex Structure Formed from the Reversed Human Telomeric DNA Sequence

by Lydia Olejko, Anushree Dutta, Kosar Shahsavar and Ilko Bald

Int. J. Mol. Sci. 2022, 23(20), 12206; https://doi.org/10.3390/ijms232012206 - 13 Oct 2022

Cited by 5 | Viewed by 1872

Abstract

G-rich telomeric DNA plays a major role in the stabilization of chromosomes and can fold into a plethora of different G-quadruplex structures in the presence of mono- and divalent cations. The reversed human telomeric DNA sequence (5′-(GGG ATT)₄; RevHumTel) was previously [...] Read more.

G-rich telomeric DNA plays a major role in the stabilization of chromosomes and can fold into a plethora of different G-quadruplex structures in the presence of mono- and divalent cations. The reversed human telomeric DNA sequence (5′-(GGG ATT)₄; RevHumTel) was previously shown to have interesting properties that can be exploited for chemical sensing and as a chemical switch in DNA nanotechnology. Here, we analyze the specific G-quadruplex structures formed by RevHumTel in the presence of K⁺, Na⁺, Mg²⁺ and Ca²⁺ cations using circular dichroism spectroscopy (CDS) and Förster resonance energy transfer (FRET) based on fluorescence lifetimes. CDS is able to reveal strand and loop orientations, whereas FRET gives information about the distances between the 5′-end and the 3′-end, and also, the number of G-quadruplex species formed. Based on this combined information we derived specific G-quadruplex structures formed from RevHumTel, i.e., a chair-type and a hybrid-type G-quadruplex structure formed in presence of K⁺, whereas Na⁺ induces the formation of up to three different G-quadruplexes (a basket-type, a propeller-type and a hybrid-type structure). In the presence of Mg²⁺ and Ca²⁺ two different parallel G-quadruplexes are formed (one of which is a propeller-type structure). This study will support the fundamental understanding of the G-quadruplex formation in different environments and a rational design of G-quadruplex-based applications in sensing and nanotechnology. Full article

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12 pages, 3898 KiB

Open AccessArticle

Lipase Catalyzed Transesterification of Model Long-Chain Molecules in Double-Shell Cellulose-Coated Oil-in-Water Emulsion Particles as Microbioreactors

by Itzhak Meir, Gilad Alfassi, Yael Arazi, Dmitry M. Rein, Ayelet Fishman and Yachin Cohen

Int. J. Mol. Sci. 2022, 23(20), 12122; https://doi.org/10.3390/ijms232012122 - 12 Oct 2022

Cited by 3 | Viewed by 1629

Abstract

Lipase-catalyzed transesterification is prevalent in industrial production and is an effective alternative to chemical catalysis. However, due to lipases’ unique structure, the reaction requires a biphasic system, which suffers from a low reaction efficiency caused by a limited interfacial area. The use of [...] Read more.

Lipase-catalyzed transesterification is prevalent in industrial production and is an effective alternative to chemical catalysis. However, due to lipases’ unique structure, the reaction requires a biphasic system, which suffers from a low reaction efficiency caused by a limited interfacial area. The use of emulsion particles was found to be an effective way to increase the surface area and activity. This research focuses on cellulose as a natural surfactant for oil-in-water emulsions and evaluates the ability of lipase, introduced into the emulsion’s aqueous phase, to integrate with the emulsion microparticles and catalyze the transesterification reaction of high molecular weight esters dissolved in the particles’ cores. Cellulose-coated emulsion particles’ morphology was investigated by light, fluorescence and cryogenic scanning electron microscopy, which reveal the complex emulsion structure. Lipase activity was evaluated by measuring the hydrolysis of emulsified p-nitrophenyl dodecanoate and by the transesterification of emulsified methyl laurate and oleyl alcohol dissolved in decane. Both experiments demonstrated that lipase introduced in the aqueous medium can penetrate the emulsion particles, localize at the inner oil core interface and perform effective catalysis. Furthermore, in this system, lipase successfully catalyzed a transesterification reaction rather than hydrolysis, despite the dominant presence of water. Full article

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11 pages, 6875 KiB

Open AccessArticle

The Sequence Dependent Nanoscale Structure of CENP-A Nucleosomes

by Tommy Stormberg and Yuri L. Lyubchenko

Int. J. Mol. Sci. 2022, 23(19), 11385; https://doi.org/10.3390/ijms231911385 - 27 Sep 2022

Cited by 4 | Viewed by 1269

Abstract

CENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. [...] Read more.

CENP-A is a histone variant found in high abundance at the centromere in humans. At the centromere, this histone variant replaces the histone H3 found throughout the bulk chromatin. Additionally, the centromere comprises tandem repeats of α-satellite DNA, which CENP-A nucleosomes assemble upon. However, the effect of the DNA sequence on the nucleosome assembly and centromere formation remains poorly understood. Here, we investigated the structure of nucleosomes assembled with the CENP-A variant using Atomic Force Microscopy. We assembled both CENP-A nucleosomes and H3 nucleosomes on a DNA substrate containing an α-satellite motif and characterized their positioning and wrapping efficiency. We also studied CENP-A nucleosomes on the 601-positioning motif and non-specific DNA to compare their relative positioning and stability. CENP-A nucleosomes assembled on α-satellite DNA did not show any positional preference along the substrate, which is similar to both H3 nucleosomes and CENP-A nucleosomes on non-specific DNA. The range of nucleosome wrapping efficiency was narrower on α-satellite DNA compared with non-specific DNA, suggesting a more stable complex. These findings indicate that DNA sequence and histone composition may be two of many factors required for accurate centromere assembly. Full article

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19 pages, 1637 KiB

Open AccessArticle

Formulation, Characterisation and Evaluation of the Antihypertensive Peptides, Isoleucine-Proline-Proline and Leucine-Lysine-Proline in Chitosan Nanoparticles Coated with Zein for Oral Drug Delivery

by Minna Khalid Danish, John P. Gleeson, David J. Brayden, Hugh J. Byrne, Jesus M. Frías and Sinéad M. Ryan

Int. J. Mol. Sci. 2022, 23(19), 11160; https://doi.org/10.3390/ijms231911160 - 22 Sep 2022

Cited by 9 | Viewed by 1923

Abstract

Isoleucine-Proline-Proline (IPP) and Leucine-Lysine-Proline (LKP) are food-derived tripeptides whose antihypertensive functions have been demonstrated in hypertensive rat models. However, peptides display low oral bioavailability due to poor intestinal epithelial permeability and instability. IPP and LKP were formulated into nanoparticles (NP) using chitosan (CL113) [...] Read more.

Isoleucine-Proline-Proline (IPP) and Leucine-Lysine-Proline (LKP) are food-derived tripeptides whose antihypertensive functions have been demonstrated in hypertensive rat models. However, peptides display low oral bioavailability due to poor intestinal epithelial permeability and instability. IPP and LKP were formulated into nanoparticles (NP) using chitosan (CL113) via ionotropic gelation and then coated with zein. Following addition of zein, a high encapsulation efficiency (EE) (>80%) was obtained for the NP. In simulated gastric fluid (SGF), 20% cumulative release of the peptides was achieved after 2 h, whereas in simulated intestinal fluid (SIF), ~90% cumulative release was observed after 6 h. Higher colloidal stability (39–41 mV) was observed for the coated NP compared to uncoated ones (30–35 mV). In vitro cytotoxicity studies showed no reduction in cellular viability of human intestinal epithelial Caco-2 and HepG2 liver cells upon exposure to NP and NP components. Administration of NP encapsulating IPP and LKP by oral gavage to spontaneously hypertensive rats (SHR) attenuated systolic blood pressure (SBP) for 8 h. This suggests that the NP provide appropriate release to achieve prolonged hypotensive effects in vivo. In conclusion, chitosan-zein nanoparticles (CZ NP) have potential as oral delivery system for the encapsulation of IPP and LKP. Full article

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10 pages, 3423 KiB

Open AccessArticle

Laser-Processed PEN with Au Nanowires Array: A Biocompatibility Assessment

by Jana Pryjmaková, Barbora Vokatá, Petr Slepička and Jakub Siegel

Int. J. Mol. Sci. 2022, 23(18), 10953; https://doi.org/10.3390/ijms231810953 - 19 Sep 2022

Cited by 2 | Viewed by 1208

Abstract

Although many noble metals are known for their antibacterial properties against the most common pathogens, such as Escherichia coli and Staphylococcus epidermidis, their effect on healthy cells can be toxic. For this reason, the choice of metals that preserve the antibacterial effect [...] Read more.

Although many noble metals are known for their antibacterial properties against the most common pathogens, such as Escherichia coli and Staphylococcus epidermidis, their effect on healthy cells can be toxic. For this reason, the choice of metals that preserve the antibacterial effect while being biocompatible with health cells is very important. This work aims to validate the effect of gold on the biocompatibility of Au/Ag nanowires, as assessed in our previous study. Polyethylene naphthalate (PEN) was treated with a KrF excimer laser to provide specific laser-induced periodic structures. Then, Au was deposited onto the modified PEN via a vacuum evaporation method. Atomic force microscopy and scanning electron microscopy revealed the dependence of the surface morphology on the incidence angle of the laser beam. A resazurin assay cytotoxicity test confirmed safety against healthy human cells and even cell proliferation was observed after 72 h of incubation. We have obtained satisfactory results, demonstrating that monometallic Au nanowires can be applied in biomedical applications and provide the biocompatibility of bimetallic Au/AgNWs. Full article

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25 pages, 2166 KiB

Open AccessReview

Recent Advances in Hydroxyapatite-Based Biocomposites for Bone Tissue Regeneration in Orthopedics

by Ileana Ielo, Giovanna Calabrese, Giovanna De Luca and Sabrina Conoci

Int. J. Mol. Sci. 2022, 23(17), 9721; https://doi.org/10.3390/ijms23179721 - 27 Aug 2022

Cited by 85 | Viewed by 4506

Abstract

Bone tissue is a nanocomposite consisting of an organic and inorganic matrix, in which the collagen component and the mineral phase are organized into complex and porous structures. Hydroxyapatite (HA) is the most used ceramic biomaterial since it mimics the mineral composition of [...] Read more.

Bone tissue is a nanocomposite consisting of an organic and inorganic matrix, in which the collagen component and the mineral phase are organized into complex and porous structures. Hydroxyapatite (HA) is the most used ceramic biomaterial since it mimics the mineral composition of the bone in vertebrates. However, this biomimetic material has poor mechanical properties, such as low tensile and compressive strength, which make it not suitable for bone tissue engineering (BTE). For this reason, HA is often used in combination with different polymers and crosslinkers in the form of composites to improve their mechanical properties and the overall performance of the implantable biomaterials developed for orthopedic applications. This review summarizes recent advances in HA-based biocomposites for bone regeneration, addressing the most widely employed inorganic matrices, the natural and synthetic polymers used as reinforcing components, and the crosslinkers added to improve the mechanical properties of the scaffolds. Besides presenting the main physical and chemical methods in tissue engineering applications, this survey shows that HA biocomposites are generally biocompatible, as per most in vitro and in vivo studies involving animal models and that the results of clinical studies on humans sometimes remain controversial. We believe this review will be helpful as introductory information for scientists studying HA materials in the biomedical field. Full article

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26 pages, 15564 KiB

Open AccessArticle

Size-Dependent Cytoprotective Effects of Selenium Nanoparticles during Oxygen-Glucose Deprivation in Brain Cortical Cells

by Elena G. Varlamova, Sergey V. Gudkov, Egor Y. Plotnikov and Egor A. Turovsky

Int. J. Mol. Sci. 2022, 23(13), 7464; https://doi.org/10.3390/ijms23137464 - 05 Jul 2022

Cited by 18 | Viewed by 2503

Abstract

It is known that selenium nanoparticles (SeNPs) obtained on their basis have a pleiotropic effect, inducing the process of apoptosis in tumor cells, on the one hand, and protecting healthy tissue cells from death under stress, on the other hand. It has been [...] Read more.

It is known that selenium nanoparticles (SeNPs) obtained on their basis have a pleiotropic effect, inducing the process of apoptosis in tumor cells, on the one hand, and protecting healthy tissue cells from death under stress, on the other hand. It has been established that SeNPs protect brain cells from ischemia/reoxygenation through activation of the Ca²⁺ signaling system of astrocytes and reactive astrogliosis. At the same time, for a number of particles, the limitations of their use, associated with their size, are shown. The use of nanoparticles with a diameter of less than 10 nm leads to their short life-time in the bloodstream and rapid removal by the liver. Nanoparticles larger than 200 nm activate the complement system and are also quickly removed from the blood. The effects of different-sized SeNPs on brain cells have hardly been studied. Using the laser ablation method, we obtained SeNPs of various diameters: 50 nm, 100 nm, and 400 nm. Using fluorescence microscopy, vitality tests, PCR analysis, and immunocytochemistry, it was shown that all three types of the different-sized SeNPs have a cytoprotective effect on brain cortex cells under conditions of oxygen-glucose deprivation (OGD) and reoxygenation (R), suppressing the processes of necrotic death and inhibiting different efficiency processes of apoptosis. All of the studied SeNPs activate the Ca²⁺ signaling system of astrocytes, while simultaneously inducing different types of Ca²⁺ signals. SeNPs sized at 50 nm- induce Ca²⁺ responses of astrocytes in the form of a gradual irreversible increase in the concentration of cytosolic Ca²⁺ ([Ca²⁺]_i), 100 nm-sized SeNPs induce stable Ca²⁺ oscillations without increasing the base level of [Ca²⁺]_i, and 400 nm-sized SeNPs cause mixed patterns of Ca²⁺ signals. Such differences in the level of astrocyte Ca²⁺ signaling can explain the different cytoprotective efficacy of SeNPs, which is expressed in the expression of protective proteins and the activation of reactive astrogliosis. In terms of the cytoprotective efficiency under OGD/R conditions, different-sized SeNPs can be arranged in descending order: 100 nm-sized > 400 nm-sized > 50 nm-sized. Full article

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