Papers by Mariafrancesca Cascione
Nanomaterials
The increasingly widespread use of engineered nanomaterials in many applications increases the ne... more The increasingly widespread use of engineered nanomaterials in many applications increases the need to understand the mechanisms behind their toxicity [...]
Materials
Natural halloysite clay nanotubes (HNTs) are versatile inorganic reinforcing materials for creati... more Natural halloysite clay nanotubes (HNTs) are versatile inorganic reinforcing materials for creating hybrid composites. Upon doping HNTs with polymers, coating, or loading them with bioactive molecules, the production of novel nanocomposites is possible, having specific features for several applications. To investigate HNTs composites nanostructures, AFM is a very powerful tool since it allows for performing nano-topographic and morpho-mechanical measurements in any environment (air or liquid) without treatment of samples, like electron microscopes require. In this review, we aimed to provide an overview of recent AFM investigations of HNTs and HNT nanocomposites for unveiling hidden characteristics inside them envisaging future perspectives for AFM as a smart device in nanomaterials characterization.
Ithaca: Viaggio nella Scienza, Nov 11, 2021
Materials, 2022
The use of silver nanoparticles (Ag NPs) in the biomedical field deserves a mindful analysis of t... more The use of silver nanoparticles (Ag NPs) in the biomedical field deserves a mindful analysis of the possible inflammatory response which could limit their use in the clinic. Despite the anti-cancer properties of Ag NPs having been widely demonstrated, there are still few studies concerning their involvement in the activation of specific inflammatory pathways. The inflammatory outcome depends on the synthetic route used in the NPs production, in which toxic reagents are employed. In this work, we compared two types of Ag NPs, obtained by two different chemical routes: conventional synthesis using sodium citrate and a green protocol based on leaf extracts as a source of reduction and capping agents. A careful physicochemical characterization was carried out showing spherical and stable Ag NPs with an average size between 20 nm and 35 nm for conventional and green Ag NPs respectively. Then, we evaluated their ability to induce the activation of inflammation in Human Leukemic Monocytes ...
Bioinorganic Chemistry and Applications, 2022
Among all the inorganic nanomaterials used in commercial products, industry, and medicine, the am... more Among all the inorganic nanomaterials used in commercial products, industry, and medicine, the amorphous silica nanoparticles (SiO2 NPs) appeared to be often tolerated in living organisms. However, despite several toxicity studies, some concerns about the exposure to high doses of SiO2 NPs with different sizes were raised. Then, we used the microemulsion method to obtain stable SiO2 NPs having different sizes (110 nm, 50 nm, and 25 nm). In addition, a new one-pot green synthetic route using leaves extract of Laurus nobilis was performed, obtaining monodispersed ultrasmall SiO2 NPs without the use of dangerous chemicals. The NPs achieved by microemulsion were further functionalized with amino groups making the NPs surface positively charged. Then, high doses of SiO2 NPs (1 mg/mL and 3 mg/mL) achieved from the two routes, having different sizes and surface charges, were used to assess their impact on human alveolar cells (A549), being the best cell model mimicking the inhalation route...
Oligonucleotide primer sequences for SybrGreen qRT-PCR. Figure S1a–d Adhesion, migration and inva... more Oligonucleotide primer sequences for SybrGreen qRT-PCR. Figure S1a–d Adhesion, migration and invasion ability of PT45 and T3M4 shENO1 PDA cells. Adhesive potential of shENO1 PT45 (a) and shENO1 T3M4 (b) compared to relative shCTRL control cells was evaluated by culturing cells for 1 h on FN, Col-I, Col-IV and VN. Adherent cells were fixed with 2% glutaraldehyde in PBS and visualized by staining with crystal violet. For quantitative analysis, cells were treated with 10% acetic acid and elutes were read with a microplate reader at a wavelength of 570 nm. Results are expressed as Δ ⋿ OD (Optical Density) units = (OD substrate adherent cells) – (OD plastic adherent cells). (c) Migration ability was evaluated in terms of ability to close the wound with shENO1 PT45 and shENO1 T3M4 cells compared to shCTRL control cells. Representative images are shown for each condition. (d) Invasive potential of shENO1 PT45 and shENO1 T3M4 were tested by a Matrigel invasion assay, after 48 h of culture. ...
Cancers, 2021
Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily de... more Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing t...
Molecules, 2021
Noble metals nanoparticles (NPs) and metal oxide NPs are widely used in different fields of appli... more Noble metals nanoparticles (NPs) and metal oxide NPs are widely used in different fields of application and commercial products, exposing living organisms to their potential adverse effects. Recent evidences suggest their presence in the aquifers water and consequently in drinking water. In this work, we have carefully synthesized four types of NPs, namely, silver and gold NPs (Ag NPs and Au NPs) and silica and titanium dioxide NPs (SiO2 NPs and TiO2 NPs) having a similar size and negatively charged surfaces. The synthesis of Ag NPs and Au NPs was carried out by colloidal route using silver nitrate (AgNO3) and tetrachloroauric (III) acid (HAuCl4) while SiO2 NPs and TiO2 NPs were achieved by ternary microemulsion and sol-gel routes, respectively. Once the characterization of NPs was carried out in order to assess their physico-chemical properties, their impact on living cells was studied. We used the human colorectal adenocarcinoma cells (Caco-2), known as the best representative int...
Nanomedicine, 2020
Clays are mineral materials that have raised great interest in the scientific community due to th... more Clays are mineral materials that have raised great interest in the scientific community due to their low toxicity for both living organisms and the environment, making them suitable agents in nanomedical applications. "
Nanomaterials, 2020
In the last years, there is a growing interest in the application of nanoscaled materials in canc... more In the last years, there is a growing interest in the application of nanoscaled materials in cancer therapy because of their unique physico-chemical properties. However, the dark side of their usability is limited by their possible toxic behaviour and accumulation in living organisms. Starting from this assumption, the search for a green alternative to produce nanoparticles (NPs) or the discovery of green molecules, is a challenge in order to obtain safe materials. In particular, gold (Au NPs) and silver (Ag NPs) NPs are particularly suitable because of their unique physico-chemical properties, in particular plasmonic behaviour that makes them useful as active anticancer agents. These NPs can be obtained by green approaches, alternative to conventional chemical methods, owing to the use of phytochemicals, carbohydrates, and other biomolecules present in plants, fungi, and bacteria, reducing toxic effects. In addition, we analysed the use of green and stimuli-responsive polymeric bio...
Frontiers in Bioengineering and Biotechnology, 2020
In the last decade, the onset of neurodegenerative (ND) diseases is strongly widespread due to th... more In the last decade, the onset of neurodegenerative (ND) diseases is strongly widespread due to the age increase of the world population. Despite the intensive investigations boosted by the scientific community, an efficacious therapy has not been outlined yet. The drugs commonly used are only able to relieve symptom severity; following their oral or intravenous administration routes, their effectiveness is strictly limited due to their low ability to reach the Central Nervous System (CNS) overcoming the Blood Brain Barrier (BBB). Starting from these assumptions, the engineered-nanocarriers, such as lipid-nanocarriers, are suitable agents to enhance the delivery of drugs into the CNS due to their high solubility, bioavailability, and stability. Liposomal delivery systems are considered to be the ideal carriers, not only for conventional drugs but also for neuroprotective small molecules and green-extracted compounds. In the current work, the LP-based drug delivery improvements in in vivo applications against ND disorders were carefully assessed.
International Journal of Molecular Sciences, 2019
The side effects induced by nanoparticle exposure at a cellular level are one of the priority res... more The side effects induced by nanoparticle exposure at a cellular level are one of the priority research topics due to the steady increase in the use of nanoparticles (NPs). Recently, the focus on cellular morphology and mechanical behavior is gaining relevance in order to fully understand the cytotoxic mechanisms. In this regard, we have evaluated the morphomechanical alteration in human breast adenocarcinoma cell line (MCF-7) exposed to TiO2NPs at two different concentrations (25 and 50 µg/mL) and two time points (24 and 48 h). By using confocal and atomic force microscopy, we demonstrated that TiO2NP exposure induces significant alterations in cellular membrane elasticity, due to actin proteins rearrangement in cytoskeleton, as calculated in correspondence to nuclear and cytoplasmic compartments. In this work, we have emphasized the alteration in mechanical properties of the cellular membrane, induced by nanoparticle exposure.
Molecules, 2019
Lauric acid is a green derivate that is abundant in some seeds such as coconut oil where it repre... more Lauric acid is a green derivate that is abundant in some seeds such as coconut oil where it represents the most relevant fatty acid. Some studies have emphasized its anticancer effect due to apoptosis induction. In addition, the lauric acid is a Phase Change Material having a melting temperature of about 43.2 °C: this property makes it a powerful tool in cancer treatment by hyperthermal stress, generally induced at 43 °C. However, the direct use of lauric acid can have some controversial effects, and it can undergo degradation phenomena in the extracellular environment. For this reason, we have encapsulated lauric acid in a silica shell with a one-step and reproducible synthetic route in order to obtain a monodispersed SiO2@LA NPs with a good encapsulation efficiency. We have used these NPs to expose breast cancer cell lines (MCF-7) at different concentrations in combination with hyperthermal treatment. Uptake, viability, oxidative stress induction, caspases levels, and morphometric...
Nanoscale Research Letters, 2019
The nowadays growing use of nanoparticles (NPs) in commercial products does not match a comprehen... more The nowadays growing use of nanoparticles (NPs) in commercial products does not match a comprehensive understanding of their potential harmfulness. More in vitro investigations are required to address how the physicochemical properties of NPs guide their engulfment within cells and their intracellular trafficking, fate, and toxicity. These nano-bio interactions have not been extensively addressed yet, especially from a mechanical viewpoint. Cell mechanic is a critical indicator of cell health because it regulates processes like cell migration, tissue integrity, and differentiation via cytoskeleton rearrangements. Here, we investigated in vitro the elasticity perturbation of Caco-2 and A549 cell lines, in terms of Young's modulus modification induced by SiO 2 NP S and TiO 2 NP S. TiO 2 NPs demonstrated stronger effects on cell elasticity compared to SiO 2 NPs, as they induced significant morphological and morphometric changes in actin network. TiO 2 NP S increased the elasticity in Caco-2 cells, while opposite effects have been observed on A549 cells. These results demonstrate the existence of a correlation between the alteration of cell elasticity and NPs toxicity that depends, in turn, on the NPs physicochemical properties and the specific cell tested.
International Journal of Molecular Sciences, 2018
The epithelial mesenchymal transition (EMT) is a physiological multistep process involving epithe... more The epithelial mesenchymal transition (EMT) is a physiological multistep process involving epithelial cells acquiring a mesenchymal-like phenotype. It is widely demonstrated that EMT is linked to tumor progression and metastasis. The transforming growth factor (TGF)-β pathways have been widely investigated, but its role in the hepatocarcinoma EMT is still unclear. While the biochemical pathways have been extensively studied, the alteration of biomechanical behavior correlated to cellular phenotype and motility is not yet fully understood. To better define the involvement of TGF-β1 in the metastatic progression process in different hepatocarcinoma cell lines (HepG2, PLC/PRF/5, HLE), we applied a systematic morphomechanical approach in order to investigate the physical and the structural characteristics. In addition, we evaluated the antitumor effect of LY2157299, a TGF-βR1 kinase inhibitor, from a biomechanical point of view, using Atomic Force and Confocal Microscopy. Our approach a...
Journal of Nanoparticle Research, 2018
The unique physico-chemical properties of silver nanoparticles (AgNPs) make them a powerful tool ... more The unique physico-chemical properties of silver nanoparticles (AgNPs) make them a powerful tool in many fields, ranging from cosmetics, biomedicals, household products, and wound dressing. Several evidences suggest the strong toxicity of AgNPs both in vitro and in vivo, but few data are available to full understanding of their adverse effects on cellular components and cytoskeleton. In this work, we assessed the toxicity of citrate-capped AgNPs on cortical actin and organelles, namely mitochondria and lysosomes, on epithelial breast cancer cells (MCF-7). The impact of AgNPs on cells was firstly evaluated in term of viability, oxidative stress, mitochondria membrane potential alteration, and apoptosis activation. Afterwards, we carefully estimated the qualitative and quantitative morphological alterations of cortical F-actin and organelles by confocal microscopy and specific software tools, coupled with a biomechanical analysis by atomic force microscopy (AFM). This multidisciplinary approach, which combines the standard biological assays with systematic morphometric and biomechanical analysis on cells, permits to understand at different levels the intracellular response elicited by AgNPs in order to provide new scenarios in toxicity assessment.
Journal of healthcare engineering, 2018
In this work, tunable nonwoven mats based on poly(3-hydroxybutyrate) (PHB) and type I collagen (C... more In this work, tunable nonwoven mats based on poly(3-hydroxybutyrate) (PHB) and type I collagen (Coll) were successfully produced by electrospinning. The PHB/Coll weight ratio (fixed at 100/0, 70/30, and 50/50, resp.) was found to control the morphological, thermal, mechanical, and degradation properties of the mats. Increasing collagen amounts led to larger diameters of the fibers (in the approximate range 600-900 nm), while delaying their thermal decomposition (from 245°C to 262°C). Collagen also accelerated the hydrolytic degradation of the mats upon incubation in aqueous medium at 37°C for 23 days (with final weight losses of 1%, 15%, and 23% for 100/0, 70/30, and 50/50 samples, resp.), as a result of increased mat wettability and reduced PHB crystallinity. Interestingly, 70/30 meshes were the ones displaying the lowest stiffness (~116 MPa; < 0.05 versus 100/0 and 50/50 meshes), while 50/50 samples had an elastic modulus comparable to that of 100/0 ones (~250 MPa), likely due ...
Cancers, Jan 16, 2018
The Epithelial to mesenchymal transition (EMT) is the process that drives epithelial tumor cells ... more The Epithelial to mesenchymal transition (EMT) is the process that drives epithelial tumor cells to acquire an invasive phenotype. The role of transforming growth factor-β1 (TGF-β1) in EMT is still debated. We used confocal laser scanning microscopy and scanning force spectroscopy to perform a morphomechanical analysis on epithelial breast cancer cells (MCF-7), comparing them before and after TGF-β1 exogenous stimulation (5 ng/mL for 48 h). After TGF-β1 treatment, loss of cell⁻cell adherence (mainly due to the reduction of E-cadherin expression of about 24%) and disaggregation of actin cortical fibers were observed in treated MCF-7. In addition, TGF-β1 induced an alteration of MCF-7 nuclei morphology as well as a decrease in the Young's modulus, owing to a rearrangement that involved the cytoskeletal networks and the nuclear region. These relevant variations in morphological features and mechanical properties, elicited by TGF-β1, suggested an increased capacity of MCF-7 to migra...
Nanomaterials (Basel, Switzerland), Jan 10, 2018
The large use of nanomaterials in many fields of application and commercial products highlights t... more The large use of nanomaterials in many fields of application and commercial products highlights their potential toxicity on living organisms and the environment, despite their physico-chemical properties. Among these, silver nanoparticles (Ag NPs) are involved in biomedical applications such as antibacterial agents, drug delivery vectors and theranostics agents. In this review, we explain the common synthesis routes of Ag NPs using physical, chemical, and biological methods, following their toxicity mechanism in cells. In particular, we analyzed the physiological cellular pathway perturbations in terms of oxidative stress induction, mitochondrial membrane potential alteration, cell death, apoptosis, DNA damage and cytokines secretion after Ag NPs exposure. In addition, their potential anti-cancer activity and theranostic applications are discussed.
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Papers by Mariafrancesca Cascione