Research

16 pages, 3217 KiB

Open AccessArticle

Silica Nanoparticle Internalization Improves Chemotactic Behaviour of Human Mesenchymal Stem Cells Acting on the SDF1α/CXCR4 Axis

by Emanuela Vitale, Daniela Rossin, Sadia Perveen, Ivana Miletto, Marco Lo Iacono, Raffaella Rastaldo and Claudia Giachino

Biomedicines 2022, 10(2), 336; https://doi.org/10.3390/biomedicines10020336 - 01 Feb 2022

Cited by 6 | Viewed by 1786

Abstract

Human mesenchymal stem cell (hMSC)-based therapy is an emerging resource in regenerative medicine. Despite the innate ability of hMSCs to migrate to sites of injury, homing of infused hMSCs to the target tissue is inefficient. It was shown that silica nanoparticles (SiO₂ [...] Read more.

Human mesenchymal stem cell (hMSC)-based therapy is an emerging resource in regenerative medicine. Despite the innate ability of hMSCs to migrate to sites of injury, homing of infused hMSCs to the target tissue is inefficient. It was shown that silica nanoparticles (SiO₂-NPs), previously developed to track the stem cells after transplantation, accumulated in lysosomes leading to a transient blockage of the autophagic flux. Since CXCR4 turnover is mainly regulated by autophagy, we tested the effect of SiO₂-NPs on chemotactic migration of hMSCs along the SDF1α/CXCR4 axis that plays a pivotal role in directing MSC homing to sites of injury. Our results showed that SiO₂-NP internalization augmented CXCR4 surface levels. We demonstrated that SiO₂-NP-dependent CXCR4 increase was transient, and it reversed at the same time as lysosomal compartment normalization. Furthermore, the autophagy inhibitor Bafilomycin-A1 reproduced CXCR4 overexpression in control hMSCs confirming the direct effect of the autophagic degradation blockage on CXCR4 expression. Chemotaxis assays showed that SiO₂-NPs increased hMSC migration toward SDF1α. In contrast, migration improvement was not observed in TNFα/TNFR axis, due to the proteasome-dependent TNFR regulation. Overall, our findings demonstrated that SiO₂-NP internalization increases the chemotactic behaviour of hMSCs acting on the SDF1α/CXCR4 axis, unmasking a high potential to improve hMSC migration to sites of injury and therapeutic efficacy upon cell injection in vivo. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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13 pages, 5352 KiB

Open AccessArticle

Mitoxantrone-Loaded Nanoferritin Slows Tumor Growth and Improves the Overall Survival Rate in a Subcutaneous Pancreatic Cancer Mouse Model

by Giamaica Conti, Martina Pitea, Riccardo Ossanna, Roberta Opri, Giada Tisci, Elisabetta Falvo, Giulio Innamorati, Esther Ghanem, Andrea Sbarbati, Pierpaolo Ceci and Giulio Fracasso

Biomedicines 2021, 9(11), 1622; https://doi.org/10.3390/biomedicines9111622 - 05 Nov 2021

Cited by 2 | Viewed by 1887

Abstract

Pancreatic cancer (PC) represents an intriguing topic for researchers. To date, the prognosis of metastasized PC is poor with just 7% of patients exceeding a five-year survival period. Thus, molecular modifications of existing drugs should be developed to change the course of the [...] Read more.

Pancreatic cancer (PC) represents an intriguing topic for researchers. To date, the prognosis of metastasized PC is poor with just 7% of patients exceeding a five-year survival period. Thus, molecular modifications of existing drugs should be developed to change the course of the disease. Our previously generated nanocages of Mitoxantrone (MIT) encapsulated in human H-chain Ferritin (HFt), designated as HFt-MP-PASE-MIT, has shown excellent tumor distribution and extended serum half-life meriting further investigation for PC treatment. Thus, in this study, we used the same nano-formulation to test its cytotoxicity using both in vitro and in vivo assays. Interestingly, both encapsulated and free-MIT drugs demonstrated similar killing capabilities on PaCa44 cell line. Conversely, in vivo assessment in a subcutaneous PaCa44 tumor model of PC demonstrated a remarkable capability for encapsulated MIT to control tumor growth and improve mouse survival with a median survival rate of 65 vs. 33 days for loaded and free-MIT, respectively. Interestingly, throughout the course of mice treatment, MIT encapsulation did not present any adverse side effects as confirmed by histological analysis of various murine tissue organs and body mass weights. Our results are promising and pave the way to effective PC targeted chemotherapy using our HFt nanodelivery platforms. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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12 pages, 1406 KiB

Open AccessArticle

Impact of Viral Decontamination Method on Cytokine Profile of COVID-19 Patients

by Davide Magrì, Anna Navarro, Federica Bergami, Elena Percivalle, Alessandro Ferrari, Teresa Lettieri, Luigi Calzolai, Antonio Piralla, Fausto Baldanti and Sabrina Gioria

Biomedicines 2021, 9(10), 1287; https://doi.org/10.3390/biomedicines9101287 - 22 Sep 2021

Viewed by 2139

Abstract

COVID-19 related morbidity and mortality have been often attributed to an exaggerated immune response. The role of cytokines and chemokines in COVID-19 and their contributions to illness severity are known, and thus their profiling from patient bronchoalveolar lavage (BAL) samples would help in [...] Read more.

COVID-19 related morbidity and mortality have been often attributed to an exaggerated immune response. The role of cytokines and chemokines in COVID-19 and their contributions to illness severity are known, and thus their profiling from patient bronchoalveolar lavage (BAL) samples would help in understanding the disease progression. To date, limited studies have been performed on COVID-19 BAL samples, as the manipulation of such specimens (potentially containing live viruses) requires several laboratorial precautions, such as personnel training and special equipment, a requirement that not all laboratories can fulfil. Here, we assessed two fast and easily applicable methods (ultrafiltration and ultraviolet–C irradiation) for their impact on viral load removal or inactivation, respectively and on cytokine profiles preservation. Eight samples of BAL fluids from SARS-CoV2 patients with high viral load were tested. For both methods, complete removal was confirmed by lack of viral replication in Vero E6 cells and by RT-qPCR. Although both methods showed to remove completely the active SARS-CoV2 viral load, only UVC treatment has little or no quantitative effect on total cytokines/chemokines measurements, however cytokines profile and relative ratios are preserved or minimally altered when compared data obtained by the two different decontamination methods. Sample preparation and manipulation can greatly affect the analytical results; therefore, understanding if changes occurred after sample processing is of outmost importance for reliable data and can be useful to improve clinical practice. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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17 pages, 1970 KiB

Open AccessArticle

Targeting Cancer Cells Overexpressing Folate Receptors with New Terpolymer-Based Nanocapsules: Toward a Novel Targeted DNA Delivery System for Cancer Therapy

by Elena Bellotti, Maria Grazia Cascone, Niccoletta Barbani, Daniela Rossin, Raffaella Rastaldo, Claudia Giachino and Caterina Cristallini

Biomedicines 2021, 9(9), 1275; https://doi.org/10.3390/biomedicines9091275 - 21 Sep 2021

Cited by 24 | Viewed by 3123

Abstract

Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a [...] Read more.

Chemotherapeutics represent the standard treatment for a wide range of cancers. However, these agents also affect healthy cells, thus leading to severe off-target effects. Given the non-selectivity of the commonly used drugs, any increase in the selective tumor tissue uptake would represent a significant improvement in cancer therapy. Recently, the use of gene therapy to completely remove the lesion and avoid the toxicity of chemotherapeutics has become a tendency in oncotherapy. Ideally, the genetic material must be safely transferred from the site of administration to the target cells, without involving healthy tissues. This can be achieved by encapsulating genes into non-viral carriers and modifying their surface with ligands with high selectivity and affinity for a relevant receptor on the target cells. Hence, in this work we evaluate the use of terpolymer-based nanocapsules for the targeted delivery of DNA toward cancer cells. The surface of the nanocapsules is decorated with folic acid to actively target the folate receptors overexpressed on a variety of cancer cells. The nanocapsules demonstrate a good ability of encapsulating and releasing DNA. Moreover, the presence of the targeting moieties on the surface of the nanocapsules favors cell uptake, opening up the possibility of more effective therapies. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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17 pages, 2860 KiB

Open AccessArticle

Carbon Nanofibers versus Silver Nanoparticles: Time-Dependent Cytotoxicity, Proliferation, and Gene Expression

by Beatriz Salesa, Marcelo Assis, Juan Andrés and Ángel Serrano-Aroca

Biomedicines 2021, 9(9), 1155; https://doi.org/10.3390/biomedicines9091155 - 03 Sep 2021

Cited by 20 | Viewed by 3189

Abstract

Carbon nanofibers (CNFs) are one-dimensional nanomaterials with excellent physical and broad-spectrum antimicrobial properties characterized by a low risk of antimicrobial resistance. Silver nanoparticles (AgNPs) are antimicrobial metallic nanomaterials already used in a broad range of industrial applications. In the present study these two [...] Read more.

Carbon nanofibers (CNFs) are one-dimensional nanomaterials with excellent physical and broad-spectrum antimicrobial properties characterized by a low risk of antimicrobial resistance. Silver nanoparticles (AgNPs) are antimicrobial metallic nanomaterials already used in a broad range of industrial applications. In the present study these two nanomaterials were characterized by Raman spectroscopy, transmission electron microscopy, zeta potential, and dynamic light scattering, and their biological properties were compared in terms of cytotoxicity, proliferation, and gene expression in human keratinocyte HaCaT cells. The results showed that both AgNPs and CNFs present similar time-dependent cytotoxicity (EC₅₀ of 608.1 µg/mL for CNFs and 581.9 µg/mL for AgNPs at 24 h) and similar proliferative HaCaT cell activity. However, both nanomaterials showed very different results in the expression of thirteen genes (superoxide dismutase 1 (SOD1), catalase (CAT), matrix metallopeptidase 1 (MMP1), transforming growth factor beta 1 (TGFB1), glutathione peroxidase 1 (GPX1), fibronectin 1 (FN1), hyaluronan synthase 2 (HAS2), laminin subunit beta 1 (LAMB1), lumican (LUM), cadherin 1 CDH1, collagen type IV alpha (COL4A1), fibrillin (FBN), and versican (VCAN)) treated with the lowest non-cytotoxic concentrations in the HaCaT cells after 24 h. The AgNPs were capable of up-regulating only two genes (SOD1 and MMP1) while the CNFs were very effective in up-regulating eight genes (FN1, MMP1, CAT, CDH1, COL4A1, FBN, GPX1, and TGFB1) involved in the defense mechanisms against oxidative stress and maintaining and repairing tissues by regulating cell adhesion, migration, proliferation, differentiation, growth, morphogenesis, and tissue development. These results demonstrate CNF nanomaterials’ unique great potential in biomedical applications such as tissue engineering and wound healing. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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9 pages, 2182 KiB

Open AccessArticle

Bovine Serum Albumin-Immobilized Black Phosphorus-Based γ-Fe₂O₃ Nanocomposites: A Promising Biocompatible Nanoplatform

by Atanu Naskar, Sohee Lee, Dongjoon Ko, Semi Kim and Kwang-sun Kim

Biomedicines 2021, 9(8), 858; https://doi.org/10.3390/biomedicines9080858 - 22 Jul 2021

Cited by 6 | Viewed by 2402

Abstract

The interactions between proteins and nanoparticles need to be fully characterized as the immobilization of proteins onto various nanoplatforms in the physiological system often results in the change of surface of the protein molecules to avoid any detrimental issues related to their biomedical [...] Read more.

The interactions between proteins and nanoparticles need to be fully characterized as the immobilization of proteins onto various nanoplatforms in the physiological system often results in the change of surface of the protein molecules to avoid any detrimental issues related to their biomedical applications. Hence, in this article, the successful low-temperature synthesis of a BP-based γ-Fe₂O₃ (IB) nanocomposite and its interactive behavior with bovine serum albumin (BSA)—a molecule with chemical similarity and high sequence identity to human serum albumin—are described. To confirm the formation of γ-Fe₂O₃ and the IB nanocomposite, X-ray diffraction, transmission electron microscopy, and X-ray photoelectron spectroscopy analyses of the materials were performed. Additionally, the physical interaction between BSA and the IB nanocomposite was confirmed via UV–Vis and photoluminescence spectral analyses. Finally, the biocompatibility of the BSA-immobilized IB nanocomposite was verified using an in vitro cytotoxicity assay with HCT-15 colon cancer cells. Our findings demonstrate that this newly developed nanocomposite has potential utility as a biocompatible nanoplatform for various biomedical applications. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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33 pages, 17188 KiB

Open AccessArticle

Local Delivery of Pirfenidone by PLA Implants Modifies Foreign Body Reaction and Prevents Fibrosis

by Alexey Fayzullin, Semyon Churbanov, Natalia Ignatieva, Olga Zakharkina, Mark Tokarev, Daniil Mudryak, Yana Khristidis, Maxim Balyasin, Alexandr Kurkov, Elena N. Golubeva, Nadejda A. Aksenova, Tatyana Dyuzheva, Peter Timashev, Anna Guller and Anatoly Shekhter

Biomedicines 2021, 9(8), 853; https://doi.org/10.3390/biomedicines9080853 - 21 Jul 2021

Cited by 17 | Viewed by 3385

Abstract

Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (<3 h) circulation half-life and strong adverse side effects. In the current study, [...] Read more.

Peri-implant fibrosis (PIF) increases the postsurgical risks after implantation and limits the efficacy of the implantable drug delivery systems (IDDS). Pirfenidone (PF) is an oral anti-fibrotic drug with a short (<3 h) circulation half-life and strong adverse side effects. In the current study, disk-shaped IDDS prototype combining polylactic acid (PLA) and PF, PLA@PF, with prolonged (~3 days) PF release (in vitro) was prepared. The effects of the PLA@PF implants on PIF were examined in the rabbit ear skin pocket model on postoperative days (POD) 30 and 60. Matching blank PLA implants (PLA⁰) and PLA⁰ with an equivalent single-dose PF injection performed on POD0 (PLA⁰+injPF) served as control. On POD30, the intergroup differences were observed in α-SMA, iNOS and arginase-1 expressions in PLA@PF and PLA⁰+injPF groups vs. PLA⁰. On POD60, PIF was significantly reduced in PLA@PF group. The peri-implant tissue thickness decreased (532 ± 98 μm vs. >1100 μm in control groups) approaching the intact derma thickness value (302 ± 15 μm). In PLA@PF group, the implant biodegradation developed faster, while arginase-1 expression was suppressed in comparison with other groups. This study proves the feasibility of the local control of fibrotic response on implants via modulation of foreign body reaction with slowly biodegradable PF-loaded IDDS. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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Review

Jump to: Research, Other

29 pages, 1854 KiB

Open AccessEditor’s ChoiceReview

Perspectives of Microscopy Methods for Morphology Characterisation of Extracellular Vesicles from Human Biofluids

by Mladenka Malenica, Marija Vukomanović, Mario Kurtjak, Valentina Masciotti, Simone dal Zilio, Silvio Greco, Marco Lazzarino, Vedrana Krušić, Marko Perčić, Ivana Jelovica Badovinac, Karmen Wechtersbach, Ivona Vidović, Vanja Baričević, Srećko Valić, Pero Lučin, Nika Kojc and Kristina Grabušić

Biomedicines 2021, 9(6), 603; https://doi.org/10.3390/biomedicines9060603 - 26 May 2021

Cited by 40 | Viewed by 7710

Abstract

Extracellular vesicles (EVs) are nanometric membranous structures secreted from almost every cell and present in biofluids. Because EV composition reflects the state of its parental tissue, EVs possess an enormous diagnostic/prognostic potential to reveal pathophysiological conditions. However, a prerequisite for such usage of [...] Read more.

Extracellular vesicles (EVs) are nanometric membranous structures secreted from almost every cell and present in biofluids. Because EV composition reflects the state of its parental tissue, EVs possess an enormous diagnostic/prognostic potential to reveal pathophysiological conditions. However, a prerequisite for such usage of EVs is their detailed characterisation, including visualisation which is mainly achieved by atomic force microscopy (AFM) and electron microscopy (EM). Here we summarise the EV preparation protocols for AFM and EM bringing out the main challenges in the imaging of EVs, both in their natural environment as biofluid constituents and in a saline solution after EV isolation. In addition, we discuss approaches for EV imaging and identify the potential benefits and disadvantages when different AFM and EM methods are applied, including numerous factors that influence the morphological characterisation, standardisation, or formation of artefacts. We also demonstrate the effects of some of these factors by using cerebrospinal fluid as an example of human biofluid with a simpler composition. Here presented comparison of approaches to EV imaging should help to estimate the current state in morphology research of EVs from human biofluids and to identify the most efficient pathways towards the standardisation of sample preparation and microscopy modes. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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Other

Jump to: Research, Review

12 pages, 531 KiB

Open AccessSystematic Review

Tissue Engineering of the Urethra: From Bench to Bedside

by Dusan Pastorek, Martina Culenova, Maria Csobonyeiova, Veronika Skuciova, Lubos Danisovic and Stanislav Ziaran

Biomedicines 2021, 9(12), 1917; https://doi.org/10.3390/biomedicines9121917 - 15 Dec 2021

Cited by 7 | Viewed by 2295

Abstract

Tissue engineering (TE) is a promising approach for repair/substitution of damaged tissues and organs. Urethral strictures are common and serious health conditions that impair quality of life and may lead to serious organ damage. The search for ideal materials for urethral repair has [...] Read more.

Tissue engineering (TE) is a promising approach for repair/substitution of damaged tissues and organs. Urethral strictures are common and serious health conditions that impair quality of life and may lead to serious organ damage. The search for ideal materials for urethral repair has led to interest of scientists and surgeons in urethral TE. Over the last decades, a significant amount of preclinical studies and considerable progress have been observed. In contrast, urethral TE has made slow progress in clinical practice so far. To address this, we conducted a systematic review of the literature on clinical applications of TE constructs for urethral repair in the last three decades. In summary, the TE approach is promising and effective, but many issues remain that need to be addressed for broader adoption of TE in urethral repair. Better design of trials, better cooperation of research groups and centralization could lead to reduction of costs and slowly proceed to commercialization and routine use of TE products for urethral reconstruction. Full article

(This article belongs to the Special Issue Feature Papers in "Biomedical Materials and Nanomedicine")

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