Browsing by Subject "nanoparticles"

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  • Osipova, Olga; Sharoyko, Vladimir; Zashikhina, Natalia; Zakharova, Natalya; Tennikova, Tatiana; Urtti, Arto; Korzhikova-Vlakh, Evgenia (2020)
    Polyethyleneimine, poly-L-lysine, chitosan and some others cationic polymers have been thoroughly studied as nucleic acid delivery systems in gene therapy. However, the drug release from these systems proceeds at a very low rate due to extremely high binding between a carrier and gene material. To reduce these interactions and to enhance drug release, we developed a set of amphiphilic polypeptides containing positively and negatively charged amino acids as well as a hydrophobic one. The copolymers obtained were characterized by size-exclusion chromatography, static light scattering, HPLC amino acid analysis and (HNMR)-H-1 spectroscopy. All copolymers formed particles due to a self-assembly in aqueous media. Depending on polypeptide composition, the formation of particles with hydrodynamic diameters from 180 to 900 nm was observed. Stability of polymer particles, loading and release efficiency were carefully studied. Cellular uptake of the particles was efficient and their cytotoxicity was negligible. The application of polymer carriers, containing siRNA, to vascular endothelial growth factor (VEGF-A165) silencing of ARPE-19 cells was successful. The gene silencing was confirmed by suppression of both messenger RNA and protein expression.
  • Spadaro, Maria Chiara; Zhao, Junlei; Terry, William D.; Liu, Jian; Yin, Feng; Djurabekova, Flyura; Palmer, Richard E. (2019)
    The matrix assembly cluster source (MACS) represents a bridge between conventional instruments for cluster beam deposition (CBD) and the level of industrial production. The method is based on Ar+ ion sputtering of a pre-condensed Ar-M matrix (where M, is typically a metal such as Ag). Each Ar+ ion produces a collision cascade and thus the formation of metal clusters is in the matrix, which are then sputtered out. Here we present an experimental and computational investigation of the cluster emission process, specifically its dependence on the Ar+ ion angle of incidence and the cluster emission angle. We find the incidence angle strongly influences the emerging cluster flux, which is assigned to the spatial location of the deposited primary ion energy relative to the cluster into the matrix. We also found an approximately constant angle between the incident ion beam and the peak in the emitted cluster distribution, with value between 99 degrees and 109 degrees.
  • Long, Qiang; Liu, Zehua; Shao, Qianwen; Shi, Hongpeng; Huang, Shixing; Jiang, Chenyu; Qian, Bei; Zhong, Yiming; He, Xiaojun; Xiang, Xiaogang; Yang, Yang; Li, Bing; Yan, Xiaoxiang; Zhao, Qiang; Wei, Xiaoli; Santos, Helder A.; Ye, Xiaofeng (2022)
    Fibrotic diseases remain a substantial health burden with few therapeutic approaches. A hallmark of fibrosis is the aberrant activation and accumulation of myofibroblasts, which is caused by excessive profibrotic cytokines. Conventional anticytokine therapies fail to undergo clinical trials, as simply blocking a single or several antifibrotic cytokines cannot abrogate the profibrotic microenvironment. Here, biomimetic nanoparticles based on autologous skin fibroblasts are customized as decoys to neutralize multiple fibroblast-targeted cytokines. By fusing the skin fibroblast membrane onto poly(lactic-co-glycolic) acid cores, these nanoparticles, termed fibroblast membrane-camouflaged nanoparticles (FNPs), are shown to effectively scavenge various profibrotic cytokines, including transforming growth factor-beta, interleukin (IL)-11, IL-13, and IL-17, thereby modulating the profibrotic microenvironment. FNPs are sequentially prepared into multiple formulations for different administration routines. As a proof-of-concept, in three independent animal models with various organ fibrosis (lung fibrosis, liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring organ function and indicating that FNPs are a potential broad-spectrum therapy for fibrosis management.
  • Slater, Thomas J. A.; Wang, Yi-Chi; Leteba, Gerard M.; Quiroz, Jhon; Camargo, Pedro H. C.; Haigh, Sarah J.; Allen, Christopher S. (2020)
    Single-particle reconstruction can be used to perform three-dimensional (3D) imaging of homogeneous populations of nano-sized objects, in particular viruses and proteins. Here, it is demonstrated that it can also be used to obtain 3D reconstructions of heterogeneous populations of inorganic nanoparticles. An automated acquisition scheme in a scanning transmission electron microscope is used to collect images of thousands of nanoparticles. Particle images are subsequently semi-automatically clustered in terms of their properties and separate 3D reconstructions are performed from selected particle image clusters. The result is a 3D dataset that is representative of the full population. The study demonstrates a methodology that allows 3D imaging and analysis of inorganic nanoparticles in a fully automated manner that is truly representative of large particle populations.
  • Bimbo, Luis M.; Sarparanta, Mirkka; Santos, Helder A.; Airaksinen, Anu J.; Makila, Ermei; Laaksonen, Timo; Peltonen, Leena; Lehto, Vesa-Pekka; Hirvonen, Jouni; Salonen, Jarno (AMERICAN CHEMICAL SOCIETY., 2010)
  • Bimbo, Luis M.; Sarparanta, Mirkka; Santos, Hélder A.; Airaksinen, Anu J.; Mäkilä, Ermei; Laaksonen, Timo; Peltonen, Leena; Lehto, Vesa-Pekka; Hirvonen, Jouni; Salonen, Jarno (AMERICAN CHEMICAL SOCIETY., 2010)
  • Fontana, Flavia; Albertini, Silvia; Correia, Alexandra; Kemell, Marianna Leena; Lindgren, Rici; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni Tapio; Ferrari, Franca; Almeida Santos, Helder (2018)
    Biohybrid nanosystems are at the center of personalized medicine, affording prolonged circulation time and targeting to the disease site, and serving as antigenic sources of vaccines. The optimization and functionality parameters of these nanosystems vary depending on the properties of the core particles. In this work, the effects of the core particles’ surface charge and hydrophobicity are evaluated on the nanosystem coating with vesicles derived from plasma membrane. The measured parameters are the dimensions, surface charge, shape, and stability of the biohybrid nanosystems, both in buffer and in biologically relevant media (plasma and simulated synovial fluid). Moreover, the cytocompatibility properties of the developed nanosystems are evaluated in different cell lines mimicking the target cell populations and other districts of the body involved in the distribution and elimination of the nanoparticles. Finally, the immunological profile of the particles is investigated, highlighting the absence of immune activation promoted by the nanoplatforms.
  • Mendes, Luis; Kangas, Anneli; Kukko, Kirsi; Molgaard, Bjarke; Saamanen, Arto; Kanerva, Tomi; Ituarte, Inigo Flores; Huhtiniemi, Marika; Stockmann-Juvala, Helene; Partanen, Jouni; Hämeri, Kaarle; Eleftheriadis, Konstantinos; Viitanen, Anna-Kaisa (2017)
    3D printers are currently widely available and very popular among the general public. However, the use of these devices may pose health risks to users, attributable to air-quality issues arising from gaseous and particulate emissions in particular. We characterized emissions from a low-end 3D printer based on material extrusion, using the most common polymers: acrylonitrile-butadiene-styrene (ABS) and polylactic acid (PLA). Measurements were carried out in an emission chamber and a conventional room. Particle emission rates were obtained by direct measurement and modeling, whereas the influence of extrusion temperature was also evaluated. ABS was the material with the highest aerosol emission rate. The nanoparticle emission ranged from 3.7.10(8) to 1.4.10(9) particles per second (# s(-1)) in chamber measurements and from 2.0.10(9) to 4.0.10(9) # s(-1)in room measurements, when the recommended extruder temperature was used. Printing with PLA emitted nanoparticles at the rate of 1.0.10(7) # s(-1) inside the chamber and negligible emissions in room experiments. Emission rates were observed to depend strongly on extruder temperature. The particles' mean size ranged from 7.8 to 10.5 nanometers (nm). We also detected a significant emission rate of particles of 1 to 3nm in size during all printing events. The amounts of volatile organic and other gaseous compounds were only traceable and are not expected to pose health risks. Our study suggests that measures preventing human exposure to high nanoparticle concentrations should be adopted when using low-end 3D printers.
  • Gupta, Govind; Gliga, Anda; Hedberg, Jonas; Serra, Angela; Greco, Dario; Odnevall Wallinder, Inger; Fadeel, Bengt (2020)
    Abstract The neurotoxicity of hard metal-based nanoparticles (NPs) remains poorly understood. Here, we deployed the human neuroblastoma cell line SH-SY5Y differentiated or not into dopaminergic- and cholinergic-like neurons to study the impact of tungsten carbide (WC) NPs, WC NPs sintered with cobalt (Co), or Co NPs versus soluble CoCl2. Co NPs and Co salt triggered a dose-dependent cytotoxicity with an increase in cytosolic calcium, lipid peroxidation, and depletion of glutathione (GSH). Co NPs and Co salt also suppressed glutathione peroxidase 4 (GPX4) mRNA and protein expression. Co-exposed cells were rescued by N-acetylcysteine (NAC), a precursor of GSH, and partially by liproxstatin-1, an inhibitor of lipid peroxidation. Furthermore, in silico analyses predicted a significant correlation, based on similarities in gene expression profiles, between Co-containing NPs and Parkinson's disease, and changes in the expression of selected genes were validated by RT-PCR. Finally, experiments using primary human dopaminergic neurons demonstrated cytotoxicity and GSH depletion in response to Co NPs and CoCl2 with loss of axonal integrity. Overall, these data point to a marked neurotoxic potential of Co-based but not WC NPs and show that neuronal cell death may occur through a ferroptosis-like mechanism.
  • Abdelrehiem, Dina Ahmed Mosselhy; Assad, Mhd Adel; Sironen, Tarja; Elbahri, Mady (2021)
    The COVID-19 pandemic is expanding worldwide. This pandemic associated with COVID-19 placed the spotlight on how bacterial (e.g., methicillin-resistant Staphylococcus aureus) co-infections may impact responses to coronavirus. In this review the ways in which nanoparticles can contain and rapidly diagnose COVID-19 under the umbrella of nanotheranostics (i.e., smart, single agents combining nanodiagnostics and nanotherapeutics) are elaborated. The present work provides new insights into the promising incorporation of antiviral nanotheranostics into nanostructured materials, including electrospun fibers with tailored pore sizes and hydrophobicity, namely "superhydrophobic self-disinfecting electrospun facemasks/fabrics (SSEF)." SSEFs are proposed as smart alternatives to address the drawbacks of N95 respirators. The challenges of coronavirus containment are underscored, literature is reviewed, and "top-five suggestions" for containing COVID-19 are offered, including: i) preventive appraisals-avoiding needless hospital admission and practicing frequent hand washing (from 20 to 60 s). ii) Diagnostics-highly recommending nanodiagnostics, detecting COVID-19 within 10 min. iii) Therapeutics-expanding nanotherapeutics to treat COVID-19 and bacterial co-infections after safety assessments and clinical trials. iv) Multipronged and multinational, including China, collaborative appraisals. v) Humanitarian compassion to traverse this pandemic in a united way.
  • Abdelrehiem, Dina Ahmed Mosselhy; Virtanen, Jenni Maaret Elina; Kant, Ravi; He, Wei; Elbahri, Mady; Sironen, Tarja (2021)
    Every day, new information is presented with respect to how to best combat the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This manuscript sheds light on such recent findings, including new co-factors (i.e., neuropilin-1) and routes (i.e., olfactory transmucosal) allowing cell entry of SARS-CoV-2 and induction of neurological symptoms, as well as the new SARS-CoV-2 variants. We highlight the SARS-CoV-2 human-animal interfaces and elaborate containment strategies using the same vaccination (i.e., nanoparticle "NP" formulations of the BNT162b2 and mRNA-1273 vaccines) for humans, minks, raccoon dogs, cats, and zoo animals. We investigate the toxicity issues of anti-CoV NPs (i.e., plasmonic NPs and quantum dots) on different levels. Namely, nano-bio interfaces (i.e., protein corona), in vitro (i.e., lung cells) and in vivo (i.e., zebrafish embryos) assessments, and impacts on humans are discussed in a narrative supported by original figures. Ultimately, we express our skeptical opinion on the comprehensive administration of such antiviral nanotheranostics, even when integrated into facemasks, because of their reported toxicities and the different NP parameters (e.g., size, shape, surface charge, and purity and chemical composition of NPs) that govern their end toxicity. We believe that more toxicity studies should be performed and be presented, clarifying the odds of the safe administration of nanotoxocological solutions and the relief of a worried public.
  • Ferreira, Mónica P. A.; Talman, Virpi; Torrieri, Giulia; Liu, Dongfei; Marques, Gonçalo; Moslova, Karina; Liu, Zehua; Pinto, João F.; Hirvonen, Jouni; Ruskoaho, Heikki; Santos, Hélder A. (2018)
    The inability of the heart to recover from an ischemic insult leads to the formation of fibrotic scar tissue and heart failure. From the therapeutic strategies under investigation, cardiac regeneration holds the promise of restoring the full functionality of a damaged heart. Taking into consideration the presence of vast numbers of fibroblasts and myofibroblasts in the injured heart, direct fibroblast reprogramming into cardiomyocytes using small drug molecules is an attractive therapeutic option to replenish the lost cardiomyocytes. Here, a spermine-acetalated dextran-based functional nanoparticle is developed for pH-triggered drug delivery of two poorly water soluble small molecules, CHIR99021 and SB431542, both capable of increasing the efficiency of direct reprogramming of fibroblast into cardiomyocytes. Upon functionalization with polyethylene glycol and atrial natriuretic peptide, the biocompatibility of the nanosystem is improved, and the cellular interactions with the cardiac nonmyocytes are specifically augmented. The dual delivery of the compounds is verified in vitro, and the compounds exerted concomitantly anticipate biological effects by stabilizing β-catenin (CHIR99021) and by preventing translocation of Smad3 to the nucleus of (myo)fibroblasts (SB431542). These observations highlight the potential of this nanoparticle-based system toward improved drug delivery and efficient direct reprogramming of fibroblasts into cardiomyocyte-like cells, and thus, potential cardiac regeneration therapy.
  • Li, Wei; Zheng, Kai; Petrikaite, Vilma (2021)
  • Yan, Yufei; Sun, Tao; Zhang, Hongbo; Ji, Xiuling; Sun, Yulong; Zhao, Xin; Deng, Lianfu; Qi, Jin; Cui, Wenguo; Almeida Santos, Helder; Zhang, Hongyu (2019)
    Osteoarthritis has been regarded as a typical lubrication deficiency related joint disease, which is characterized by the breakdown of articular cartilage at the joint surface and the inflammation of the joint capsule. Here, inspired by the structure of the fresh euryale ferox seed that possesses a slippery aril and a hard coat containing starchy kernel, a novel superlubricated nanoparticle, namely poly (3‐sulfopropyl methacrylate potassium salt)‐grafted mesoporous silica nanoparticles (MSNs‐NH2@PSPMK), is biomimicked and synthesized via a one‐step photopolymerization method. The nanoparticles are endowed with enhanced lubrication by the grafted PSPMK polyelectrolyte polymer due to the formation of tenacious hydration layers surrounding the negative charges, and simultaneously are featured with effective drug loading and release behavior as a result of the sufficient mesoporous channels in the MSNs. When encapsulated with an anti‐inflammatory drug diclofenac sodium (DS), the lubrication capability of the superlubricated nanoparticles is improved, while the drug release rate is sustained by increasing the thickness of PSPMK layer, which is simply achieved via adjustment of the precursor monomer concentration in the photopolymerization process. Additionally, the in vitro and in vivo experimental results show that the DS‐loaded MSNs‐NH2@PSPMK nanoparticles effectively protect the chondrocytes from degeneration, and thus, inhibit the development of osteoarthritis.
  • Fontana, Flavia; Lindstedt, Hanna; Correia, Alexandra; Chiaro, Jacopo; Kari, Otto; Ndika, Joseph; Alenius, Harri; Buck, Jonas; Sieber, Sandro; Mäkilä, Ermei; Salonen, Jarno; Urtti, Arto; Cerullo, Vincenzo; Hirvonen, Jouni; Santos, Hélder A. (2020)
    Biohybrid nanosystems represent the cutting‐edge research in biofunctionalization of micro‐ and nano‐systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane‐coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell‐specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage‐mediated uptake.
  • Samanta, Sumanta; Le Joncour, Vadim; Wegrzyniak, Olivia; Rangasami, Vignesh Kumar; Ali-Loytty, Harri; Hong, Taehun; Selvaraju, Ram Kumar; Aberg, Ola; Hilborn, Jons; Laakkonen, Pirjo; Varghese, Oommen P.; Eriksson, Olof; Cabral, Horacio; Oommen, Oommen P. (2022)
    The poor permeability of theranostic agents across the blood-brain barrier (BBB) significantly hampers the development of new treatment modalities for neurological diseases. A new biomimetic nanocarrier is discovered using heparin (HP) that effectively passes the BBB and targets glioblastoma. Specifically, HP-coated gold nanoparticles (HP-AuNPs) are designed that are labeled with three different imaging modalities namely, fluorescein (FITC-HP-AuNP), radioisotope (68)Gallium (Ga-68-HP-AuNPs), and MRI active gadolinium (Gd-HP-AuNPs). The systemic infusion of FITC-HP-AuNPs in three different mouse strains (C57BL/6JRj, FVB, and NMRI-nude) displays excellent penetration and reveals uniform distribution of fluorescent particles in the brain parenchyma (69-86%) with some accumulation in neurons (8-18%) and microglia (4-10%). Tail-vein administration of radiolabeled Ga-68-HP-AuNPs in healthy rats also show Ga-68-HP-AuNP inside the brain parenchyma and in areas containing cerebrospinal fluid, such as the lateral ventricles, the cerebellum, and brain stem. Finally, tail-vein administration of Gd-HP-AuNPs (that displays approximate to threefold higher relaxivity than that of commercial Gd-DTPA) in an orthotopic glioblastoma (U87MG xenograft) model in nude mice demonstrates enrichment of T1-contrast at the intracranial tumor with a gradual increase in the contrast in the tumor region between 1 and 3 h. It is believed, the finding offers the untapped potential of HP-derived-NPs to deliver cargo molecules for treating neurological disorders.
  • Oroojalian, Fatemeh; Beygi, Mohammad; Baradaran, Behzad; Mokhtarzadeh, Ahad; Shahbazi, Mohammad-Ali (2021)
    Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.
  • Fontana, Flavia; Lindstedt, Hanna; Correia, Alexandra; Chiaro, Jacopo; Kari, Otto; Ndika, Joseph; Alenius, Harri; Buck, Jonas; Sieber, Sandro; Mäkilä, Ermei; Salonen, Jarno; Urtti, Arto; Cerullo, Vincenzo; Hirvonen, Jouni; Santos, Hélder A. (2020)
    Biohybrid nanosystems represent the cutting‐edge research in biofunctionalization of micro‐ and nano‐systems. Their physicochemical properties bring along advantages in the circulation time, camouflaging from the phagocytes, and novel antigens. This is partially a result of the qualitative differences in the protein corona, and the preferential targeting and uptake in homologous cells. However, the effect of the cell membrane on the cellular endocytosis mechanisms and time has not been fully evaluated yet. Here, the effect is assessed by quantitative flow cytometry analysis on the endocytosis of hydrophilic, negatively charged porous silicon nanoparticles and on their membrane‐coated counterparts, in the presence of chemical inhibitors of different uptake pathways. Principal component analysis is used to analyze all the data and extrapolate patterns to highlight the cell‐specific differences in the endocytosis mechanisms. Furthermore, the differences in the composition of static protein corona between naked and coated particles are investigated together with how these differences affect the interaction with human macrophages. Overall, the presence of the cell membrane only influences the speed and the entity of nanoparticles association with the cells, while there is no direct effect on the endocytosis pathways, composition of protein corona, or any reduction in macrophage‐mediated uptake.
  • Elbadri, Khalil (Helsingin yliopisto, 2020)
    An increased attention has been drawn towards porous silicon (PSi) based materials for biomedical applications, due to their promising features demonstrated through several scientific studies. Here, we further investigated the biological responses of PSi nanoparticles (NPs) with different surface chemistries, including immunomodulatory effects, inflammation mitigation and biocompatibility. In this collaborative study, the PSi NPs were investigated both in vitro and in vivo, using different molecular biology and biochemistry techniques, e.g., qPCR, ELISA, cell sorting and cell viability assays. Our results showed the capabilities of these PSi NPs to relieve the inflammatory conditions, whereas significant decrease was recorded of pro-inflammatory cytokines: TNF-α, IL-1β and IL-6. Likewise, these PSi NPs revealed a considerable consumption aptitude of pro-inflammatory reactive oxygen species molecules. Administrating PSi NPs in an acute liver inflammation (ALI) model, showed no conspicuous influence on cellular viability. Thus, the outcome of this study demonstrates the potential biocompatibility of PSi nanomaterials, in addition to their outstanding features as potential candidates for further incorporating in ALI applications.
  • Ji, Jianfeng; Ma, Fei; Zhang, Hongbo; Liu, Fengyong; He, Jian; Li, Wanlin; Xie, Tingting; Zhong, Danni; Zhang, Tingting; Tian, Mei; Zhang, Hong; Almeida Santos, Helder; Zhou, Min (2018)
    Triple‐negative breast cancer (TNBC) is a kind of aggressive malignancy with fast metastatic behavior. Herein, a nanosystem loaded with a near‐infrared (NIR) agent is developed to achieve chemo‐photothermal combination therapy for inhibiting tumor growth and metastasis in TNBC. The NIR agent of ultrasmall sized copper sulfide nanodots with strong NIR light‐absorbing capability is entrapped into the doxorubicin‐contained temperature‐sensitive polymer‐based nanosystem by a self‐assembled method. The temperature sensitive nanoclusters (TSNCs) can significantly enhance the drug penetration depth and significantly kill the cancer cells under the near‐infrared laser irradiation. Importantly, it is plausible that the tumor penetrating nanosystem combined with NIR laser irradiation can prevent lung and liver metastasis via extermination of the cancer stem cells. The in vivo characteristics, evaluated by photoacoustic imaging, pharmacokinetics, and biodistribution, confirm their feasibility for tumor treatment owing to their long blood circulation time and high tumor uptake. Thanks to the high tumor uptake and highly potent antitumor efficacy, the doxorubicin‐induced cardiotoxicity can be avoided when the TSNC is used. Taken together, it is believed that the nanosystem has excellent potential for clinical translation.