International Journal of Molecular Sciences

Editorial

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3 pages, 185 KiB

Open AccessEditorial

Nanomaterials in Biomedicine 2022

by Daniel Arcos

Int. J. Mol. Sci. 2023, 24(10), 9026; https://doi.org/10.3390/ijms24109026 - 19 May 2023

Cited by 1 | Viewed by 1142

Abstract

Nanomaterials in biomedicine are materials designed at a scale of 1–100 nanometers that make it possible to diagnose, treat and prevent diseases using tools and knowledge of the human body at the molecular scale [...] Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

Research

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15 pages, 4530 KiB

Open AccessArticle

Activated Carbon-Enriched Electrospun-Produced Scaffolds for Drug Delivery/Release in Biological Systems

by Zhanna K. Nazarkina, Alena O. Stepanova, Boris P. Chelobanov, Ren I. Kvon, Pavel A. Simonov, Andrey A. Karpenko and Pavel P. Laktionov

Int. J. Mol. Sci. 2023, 24(7), 6713; https://doi.org/10.3390/ijms24076713 - 04 Apr 2023

Cited by 4 | Viewed by 1506

Abstract

To vectorize drug delivery from electrospun-produced scaffolds, we introduce a thin outer drug retention layer produced by electrospinning from activated carbon nanoparticles (ACNs)-enriched polycaprolacton (PCL) suspension. Homogeneous or coaxial fibers filled with ACNs were produced by electrospinning from different PCL-based suspensions. Stable ACN [...] Read more.

To vectorize drug delivery from electrospun-produced scaffolds, we introduce a thin outer drug retention layer produced by electrospinning from activated carbon nanoparticles (ACNs)-enriched polycaprolacton (PCL) suspension. Homogeneous or coaxial fibers filled with ACNs were produced by electrospinning from different PCL-based suspensions. Stable ACN suspensions were selected by sorting through solvents, stabilizers and auxiliary components. The ACN-enriched scaffolds produced were characterized for fiber diameter, porosity, pore size and mechanical properties. The scaffold structure was analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. It was found that ACNs were mainly coated with a polymer layer for both homogeneous and coaxial fibers. Drug binding and release from the scaffolds were tested using tritium-labeled sirolimus. We showed that the kinetics of sirolimus binding/release by ACN-enriched scaffolds was determined by the fiber composition and differed from that obtained with a free ACN. ACN-enriched scaffolds with coaxial and homogeneous fibers had a biocompatibility close to scaffold-free AC, as was shown by the cultivation of human gingival fibroblasts and umbilical vein cells on scaffolds. The data obtained demonstrated that ACN-enriched scaffolds had good physico-chemical properties and biocompatibility and, thus, could be used as a retaining layer for vectored drug delivery. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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17 pages, 8594 KiB

Open AccessArticle

Rapamycin Perfluorocarbon Nanoparticle Mitigates Cisplatin-Induced Acute Kidney Injury

by Qingyu Zhou, James D. Quirk, Ying Hu, Huimin Yan, Joseph P. Gaut, Christine T. N. Pham, Samuel A. Wickline and Hua Pan

Int. J. Mol. Sci. 2023, 24(7), 6086; https://doi.org/10.3390/ijms24076086 - 23 Mar 2023

Cited by 4 | Viewed by 1660

Abstract

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10–20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and [...] Read more.

For nearly five decades, cisplatin has played an important role as a standard chemotherapeutic agent and been prescribed to 10–20% of all cancer patients. Although nephrotoxicity associated with platinum-based agents is well recognized, treatment of cisplatin-induced acute kidney injury is mainly supportive and no specific mechanism-based prophylactic approach is available to date. Here, we postulated that systemically delivered rapamycin perfluorocarbon nanoparticles (PFC NP) could reach the injured kidneys at sufficient and sustained concentrations to mitigate cisplatin-induced acute kidney injury and preserve renal function. Using fluorescence microscopic imaging and fluorine magnetic resonance imaging/spectroscopy, we illustrated that rapamycin-loaded PFC NP permeated and were retained in injured kidneys. Histologic evaluation and blood urea nitrogen (BUN) confirmed that renal structure and function were preserved 48 h after cisplatin injury. Similarly, weight loss was slowed down. Using western blotting and immunofluorescence staining, mechanistic studies revealed that rapamycin PFC NP significantly enhanced autophagy in the kidney, reduced the expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), as well as decreased the expression of the apoptotic protein Bax, all of which contributed to the suppression of apoptosis that was confirmed with TUNEL staining. In summary, the delivery of an approved agent such as rapamycin in a PFC NP format enhances local delivery and offers a novel mechanism-based prophylactic therapy for cisplatin-induced acute kidney injury. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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11 pages, 3669 KiB

Open AccessArticle

Facet-Dependent SERS Activity of Co₃O₄

by Yibo Feng, Jiaxing Wang, Jixiang Hou, Xu Zhang, Yuhang Gao and Kaiwen Wang

Int. J. Mol. Sci. 2022, 23(24), 15930; https://doi.org/10.3390/ijms232415930 - 14 Dec 2022

Cited by 4 | Viewed by 1225

Abstract

Surface-enhanced Raman spectroscopy (SERS) is an ultra-sensitive and rapid technique that is able to significantly enhance the Raman signals of analytes absorbed on functional substrates by orders of magnitude. Recently, semiconductor-based SERS substrates have shown rapid progress due to their great cost-effectiveness, stability [...] Read more.

Surface-enhanced Raman spectroscopy (SERS) is an ultra-sensitive and rapid technique that is able to significantly enhance the Raman signals of analytes absorbed on functional substrates by orders of magnitude. Recently, semiconductor-based SERS substrates have shown rapid progress due to their great cost-effectiveness, stability and biocompatibility. In this work, three types of faceted Co₃O₄ microcrystals with dominantly exposed {100} facets, {111} facets and co-exposed {100}-{111} facets (denoted as C-100, C-111 and C-both, respectively) are utilized as SERS substrates to detect the rhodamine 6G (R6G) molecule and nucleic acids (adenine and cytosine). C-100 exhibited the highest SERS sensitivity among these samples, and the lowest detection limits (LODs) to R6G and adenine can reach 10⁻⁷ M. First-principles density functional theory (DFT) simulations further unveiled a stronger photoinduced charge transfer (PICT) in C-100 than in C-111. This work provides new insights into the facet-dependent SERS for semiconductor materials. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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18 pages, 6003 KiB

Open AccessArticle

In Vitro and In Vivo Response of Zinc-Containing Mesoporous Bioactive Glasses in a Sheep Animal Model

by Javier Jiménez-Holguín, Daniel Arcos, Daniel Lozano, Melchor Saiz-Pardo, David de Pablo, Luis Ortega, Silvia Enciso, Blanca Fernández-Tomé, Idoia Díaz-Güemes, Francisco Miguel Sánchez-Margallo, Laura Casarrubios, María Teresa Portolés and María Vallet-Regí

Int. J. Mol. Sci. 2022, 23(22), 13918; https://doi.org/10.3390/ijms232213918 - 11 Nov 2022

Cited by 4 | Viewed by 1273

Abstract

Zinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models. In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for [...] Read more.

Zinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models. In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for their osteogenic activity both in vitro and in vivo. The ZnO MBGs showed excellent textural properties despite ZnO incorporation. However, the release of Zn²⁺ ions inhibited the mineralization process when immersed in simulated body fluid. In vitro assays showed significantly higher values of viability and expression of early markers of cell differentiation and angiogenesis in a ZnO-content-dependent manner. The next step was to study the osteogenic potential in a sheep bone defect model. Despite their excellent textural properties and cellular response in vitro, the ZnO MBGs were not able to integrate into the bone tissue, which can be explained in terms of inhibition of the mineralization process caused by Zn²⁺ ions. This work highlights the need to develop nanostructured materials for bone regeneration that can mineralize to interact with bone tissue and induce the processes of implant acceptance, cell colonization by osteogenic cells, and regeneration of lost bone tissue. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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18 pages, 4322 KiB

Open AccessArticle

Effects of Graphene Oxide and Reduced Graphene Oxide Nanostructures on CD4⁺ Th2 Lymphocytes

by María José Feito, Mónica Cicuéndez, Laura Casarrubios, Rosalía Diez-Orejas, Sara Fateixa, Daniela Silva, Nathalie Barroca, Paula A. A. P. Marques and María Teresa Portolés

Int. J. Mol. Sci. 2022, 23(18), 10625; https://doi.org/10.3390/ijms231810625 - 13 Sep 2022

Cited by 6 | Viewed by 1573

Abstract

The activation of T helper (Th) lymphocytes is necessary for the adaptive immune response as they contribute to the stimulation of B cells (for the secretion of antibodies) and macrophages (for phagocytosis and destruction of pathogens) and are necessary for cytotoxic T-cell activation [...] Read more.

The activation of T helper (Th) lymphocytes is necessary for the adaptive immune response as they contribute to the stimulation of B cells (for the secretion of antibodies) and macrophages (for phagocytosis and destruction of pathogens) and are necessary for cytotoxic T-cell activation to kill infected target cells. For these issues, Th lymphocytes must be converted into Th effector cells after their stimulation through their surface receptors TCR/CD3 (by binding to peptide-major histocompatibility complex localized on antigen-presenting cells) and the CD4 co-receptor. After stimulation, Th cells proliferate and differentiate into subpopulations, like Th1, Th2 or Th17, with different functions during the adaptative immune response. Due to the central role of the activation of Th lymphocytes for an accurate adaptative immune response and considering recent preclinical advances in the use of nanomaterials to enhance T-cell therapy, we evaluated in vitro the effects of graphene oxide (GO) and two types of reduced GO (rGO15 and rGO30) nanostructures on the Th2 lymphocyte cell line SR.D10. This cell line offers the possibility of studying their activation threshold by employing soluble antibodies against TCR/CD3 and against CD4, as well as the simultaneous activation of these two receptors. In the present study, the effects of GO, rGO15 and rGO30 on the activation/proliferation rate of these Th2 lymphocytes have been analyzed by studying cell viability, cell cycle phases, intracellular content of reactive oxygen species (ROS) and cytokine secretion. High lymphocyte viability values were obtained after treatment with these nanostructures, as well as increased proliferation in the presence of rGOs. Moreover, rGO15 treatment decreased the intracellular ROS content of Th2 cells in all stimulated conditions. The analysis of these parameters showed that the presence of these GO and rGO nanostructures did not alter the response of Th2 lymphocytes. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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16 pages, 2002 KiB

Open AccessArticle

Utilization of Olive Pomace in Green Synthesis of Selenium Nanoparticles: Physico-Chemical Characterization, Bioaccessibility and Biocompatibility

by Emerik Galić, Kristina Radić, Nikolina Golub, Dubravka Vitali Čepo, Nikolina Kalčec, Ena Vrček and Tomislav Vinković

Int. J. Mol. Sci. 2022, 23(16), 9128; https://doi.org/10.3390/ijms23169128 - 15 Aug 2022

Cited by 9 | Viewed by 1715

Abstract

Olive pomace extract (OPE) was investigated as a potential surface modifier for the development of the green synthesis process of selenium nanoparticles (SeNPs). In order to evaluate them as potential nutraceuticals, the obtained nanosystems were characterized in terms of size distribution, shape, zeta [...] Read more.

Olive pomace extract (OPE) was investigated as a potential surface modifier for the development of the green synthesis process of selenium nanoparticles (SeNPs). In order to evaluate them as potential nutraceuticals, the obtained nanosystems were characterized in terms of size distribution, shape, zeta potential, stability in different media, gastrointestinal bioaccessibility and biocompatibility. Systems with a unimodal size distribution of spherical particles were obtained, with average diameters ranging from 53.3 nm to 181.7 nm, depending on the type of coating agent used and the presence of OPE in the reaction mixture. The nanosystems were significantly affected by the gastrointestinal conditions. Bioaccessibility ranged from 33.57% to 56.93% and it was significantly increased by functionalization of with OPE. Biocompatibility was investigated in the HepG2 and Caco2 cell models, proving that they had significantly lower toxicity in comparison to sodium selenite. Significant differences were observed in cellular responses depending on the type of cells used, indicating differences in the mechanisms of toxicity induced by SeNPs. The obtained results provide new insight into the possibilities for the utilization of valuable food-waste extracts in the sustainable development of nanonutraceuticals. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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18 pages, 4857 KiB

Open AccessArticle

Impact of Copper-Doped Mesoporous Bioactive Glass Nanospheres on the Polymerisation Kinetics and Shrinkage Stress of Dental Resin Composites

by Danijela Marovic, Matej Par, Tobias T. Tauböck, Håvard J. Haugen, Visnja Negovetic Mandic, Damian Wüthrich, Phoebe Burrer, Kai Zheng, Thomas Attin, Zrinka Tarle and Aldo R. Boccaccini

Int. J. Mol. Sci. 2022, 23(15), 8195; https://doi.org/10.3390/ijms23158195 - 25 Jul 2022

Cited by 4 | Viewed by 1724

Abstract

We embedded copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) with antibacterial and ion-releasing properties into experimental dental composites and investigated the effect of Cu-MBGN on the polymerisation properties. We prepared seven composites with a BisGMA/TEGDMA (60/40) matrix and 65 wt.% total filler content, added [...] Read more.

We embedded copper-doped mesoporous bioactive glass nanospheres (Cu-MBGN) with antibacterial and ion-releasing properties into experimental dental composites and investigated the effect of Cu-MBGN on the polymerisation properties. We prepared seven composites with a BisGMA/TEGDMA (60/40) matrix and 65 wt.% total filler content, added Cu-MBGN or a combination of Cu-MBGN and silanised silica to the silanised barium glass base, and examined nine parameters: light transmittance, degree of conversion (DC), maximum polymerisation rate (R_max), time to reach R_max, linear shrinkage, shrinkage stress (PSS), maximum PSS rate, time to reach maximum PSS rate, and depth of cure. Cu-MBGN without silica accelerated polymerisation, reduced light transmission, and had the highest DC (58.8 ± 0.9%) and R_max (9.8 ± 0.2%/s), but lower shrinkage (3 ± 0.05%) and similar PSS (0.89 ± 0.07 MPa) versus the inert reference (0.83 ± 0.13 MPa). Combined Cu-MBGN and silica slowed the R_max and achieved a similar DC but resulted in higher shrinkage. However, using a combined 5 wt.% Cu-MBGN and silica, the PSS resembled that of the inert reference. The synergistic action of 5 wt.% Cu-MBGN and silanised silica in combination with silanised barium glass resulted in a material with the highest likelihood for dental applications in future. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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14 pages, 2875 KiB

Open AccessArticle

Design and Synthesis of Novel Raman Reporters for Bioorthogonal SERS Nanoprobes Engineering

by Caterina Dallari, Riccardo Innocenti, Elena Lenci, Andrea Trabocchi, Francesco Saverio Pavone and Caterina Credi

Int. J. Mol. Sci. 2022, 23(10), 5573; https://doi.org/10.3390/ijms23105573 - 16 May 2022

Cited by 3 | Viewed by 2052

Abstract

Surface-enhanced Raman spectroscopy (SERS) exploiting Raman reporter-labeled nanoparticles (RR@NPs) represents a powerful tool for the improvement of optical bio-assays due to RRs’ narrow peaks, SERS high sensitivity, and potential for multiplexing. In the present work, starting from low-cost and highly available raw materials [...] Read more.

Surface-enhanced Raman spectroscopy (SERS) exploiting Raman reporter-labeled nanoparticles (RR@NPs) represents a powerful tool for the improvement of optical bio-assays due to RRs’ narrow peaks, SERS high sensitivity, and potential for multiplexing. In the present work, starting from low-cost and highly available raw materials such as cysteamine and substituted benzoic acids, novel bioorthogonal RRs, characterized by strong signal (10³ counts with FWHM < 15 cm⁻¹) in the biological Raman-silent region (>2000 cm⁻¹), RRs are synthesized by implementing a versatile, modular, and straightforward method with high yields and requiring three steps lasting 18 h, thus overcoming the limitations of current reported procedures. The resulting RRs’ chemical structure has SH-pendant groups exploited for covalent conjugation to high anisotropic gold-NPs. RR@NPs constructs work as SERS nanoprobes demonstrating high colloidal stability while retaining NPs’ physical and vibrational properties, with a limit of detection down to 60 pM. RR@NPs constructs expose carboxylic moieties for further self-assembling of biomolecules (such as antibodies), conferring tagging capabilities to the SERS nanoprobes even in heterogeneous samples, as demonstrated with in vitro experiments by transmembrane proteins tagging in cell cultures. Finally, thanks to their non-overlapping spectra, we envision and preliminary prove the possibility of exploiting RR@NPs constructs simultaneously, aiming at improving current SERS-based multiplexing bioassays. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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Review

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28 pages, 2604 KiB

Open AccessReview

Mesoporous Bioactive Nanoparticles for Bone Tissue Applications

by Daniel Arcos and María Teresa Portolés

Int. J. Mol. Sci. 2023, 24(4), 3249; https://doi.org/10.3390/ijms24043249 - 07 Feb 2023

Cited by 8 | Viewed by 2481

Abstract

Research in nanomaterials with applications in bone regeneration therapies has experienced a very significant advance with the development of bioactive mesoporous nanoparticles (MBNPs). These nanomaterials consist of small spherical particles that exhibit chemical properties and porous structures that stimulate bone tissue regeneration, since [...] Read more.

Research in nanomaterials with applications in bone regeneration therapies has experienced a very significant advance with the development of bioactive mesoporous nanoparticles (MBNPs). These nanomaterials consist of small spherical particles that exhibit chemical properties and porous structures that stimulate bone tissue regeneration, since they have a composition similar to that of conventional sol–gel bioactive glasses and high specific surface area and porosity values. The rational design of mesoporosity and their ability to incorporate drugs make MBNPs an excellent tool for the treatment of bone defects, as well as the pathologies that cause them, such as osteoporosis, bone cancer, and infection, among others. Moreover, the small size of MBNPs allows them to penetrate inside the cells, provoking specific cellular responses that conventional bone grafts cannot perform. In this review, different aspects of MBNPs are comprehensively collected and discussed, including synthesis strategies, behavior as drug delivery systems, incorporation of therapeutic ions, formation of composites, specific cellular response and, finally, in vivo studies that have been performed to date. Full article

(This article belongs to the Special Issue Nanomaterials in Biomedicine 2022)

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