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•Functionalized graphene can capture viruses and deliver antiviral drugs.•Viruses on graphene can be inactivated by light or heat treatments.•Graphene can be used as coating material ...for medical devices, personal protective equipment or facemasks to minimize the risk of transmission.•Graphene-based sensors can be embedded in textiles and environmental filters or used for high-throughput screening of virus helicase inhibitors.
The pneumonia outbreak of coronavirus disease 2019 (COVID-19) represents a global issue. The bidimensional material graphene has captured much attention due to promising antimicrobial applications and has also demonstrated antiviral efficacy. In response to this global outbreak, we summarized the current state of knowledge of graphene and virus interaction as well as possible successful applications to fight COVID-19. Antibody-conjugated graphene sheets can rapidly detect targeted virus proteins and can be useful for large population screening, but also for the development of environmental sensors and filters, given the low cost of graphene materials. Functionalized graphene has demonstrated a good viral capture capacity that, combined with heat or light-mediated inactivation, could be used as a disinfectant. Graphene sensors arrays can be implemented on standard utility textiles and drug efficacy screening. Thanks to its high versatility, we foresee that graphene may have a leading role in the fight against COVID-19.
In order to pass through the microcirculation, red blood cells (RBCs) need to undergo extensive deformations and to recover the original shape. This extreme deformability is altered by various ...pathological conditions. On the other hand, an altered RBC deformability can have major effects on blood flow and can lead to pathological implications. The study of the viscoelastic response of red blood cells to mechanical stimuli is crucial to fully understand deformability changes under pathological conditions. However, the typical erythrocyte biconcave shape hints to a complex and intrinsically heterogeneous mechanical response that must be investigated by using probes at the nanoscale level. In this work, the local viscoelastic behaviour of healthy and pathological red blood cells was probed by Atomic Force Microscopy (AFM). Our results clearly show that the RBC stiffness is not spatially homogeneous, suggesting a strong correlation with the erythrocyte biconcave shape. Moreover, our nanoscale mapping highlights the key role played by viscous forces, demonstrating that RBCs do not behave as pure elastic bodies. The fundamental role played by viscous forces is further strengthened by the comparison between healthy and pathological (diabetes mellitus) RBCs. It is well known that pathological RBCs are usually stiffer than the healthy ones. Our measures unveil a more complex scenario according to which the difference between normal and pathological red blood cells does not merely lie in their stiffness but also in a different dynamical response to external stimuli that is governed by viscous forces.
SW480 and SW620 colon carcinoma cell lines derive from primary tumour and lymph-node metastasis of the same patient, respectively. For this reason, these cells represent an ideal system to analyse ...phenotypic variations associated with the metastatic process. In this study we analysed SW480 and SW620 cytoskeleton remodelling by measuring the cells' mechanics and morphological properties using different microscopic techniques. We observed that different specialized functions of cells, i.e. the capacity to metastasize of elongated cells inside the primary tumour and the ability to intravasate and resist shear forces of the stream of cells derived from lymph node metastasis, are reflected in their mechanical properties. We demonstrated that, together with stiffness and adhesion between the AFM tip and the cell surface, cell shape, actin organization and surface roughness are strictly related and are finely modulated by colorectal cancer cells to better accomplish their specific tasks in cancer growth and invasion.
Today, liposomes are an advanced technology of drug carriers with a dozen drugs in clinical practice and many more in clinical trials. A bottleneck associated with the clinical translation of ...liposomes has long been 'opsonization', i.e. the adsorption of plasma proteins at the liposome surface resulting in their rapid clearance from circulation. For decades, the most popular way to avoid opsonization has been grafting polyethylene glycol (PEG) onto the liposome surface. Recent studies have clarified that grafting PEG onto the liposome surface reduces, but does not completely prevent protein binding. In this work, we employed dynamic light scattering, zeta-potential analysis, one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE), semi-quantitative densitometry and cell imaging to explore the bio-nano-interactions between human plasma (HP) and Onivyde, a PEGylated liposomal drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of metastatic pancreatic ductal adenocarcinoma (PDAC). To properly evaluate the role of PEGylation, an unPEGylated variant of Onivyde was used as a reference. Collectively, our findings suggest that: (i) although PEGylated, Onivyde is not "stealth" in HP; (ii) surface chemistry is more important than PEGylation in controlling the bio-nano-interactions between Onivyde and plasma components. Of note is that the PC was found to boost the cellular uptake of Onivyde in the pancreas ductal adenocarcinoma cell line (PANC-1) thus suggesting its prominent role in its indication for PDAC treatment. Relevant implications for drug delivery and drug design are discussed.
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a crucial tumor suppressor protein with frequent mutations and alterations. Although protein therapeutics are already integral to ...numerous medical fields, their potential remains nascent. This study aimed to investigate the impact of stable, unphosphorylated recombinant human full-length PTEN and its truncated variants, regarding their tumor suppression activity with multiwalled-carbon nanotubes (MW-CNTs) as vehicles for their delivery in breast cancer cells (T-47D, ZR-75-1, and MCF-7). The cloning, overexpression, and purification of PTEN variants were achieved from E. coli, followed by successful binding to CNTs. Cell incubation with protein-functionalized CNTs revealed that the full-length PTEN-CNTs significantly inhibited cancer cell growth and stimulated apoptosis in ZR-75-1 and MCF-7 cells, while truncated PTEN fragments on CNTs had a lesser effect. The N-terminal fragment, despite possessing the active site, did not have the same effect as the full length PTEN, emphasizing the necessity of interaction with the C2 domain in the C-terminal tail. Our findings highlight the efficacy of full-length PTEN in inhibiting cancer growth and inducing apoptosis through the alteration of the expression levels of key apoptotic markers. In addition, the utilization of carbon nanotubes as a potent PTEN protein delivery system provides valuable insights for future applications in in vivo models and clinical studies.
Cancer is designated as one of the principal causes of mortality universally. Among different types of cancer, brain cancer remains the most challenging one due to its aggressiveness, the ineffective ...permeation ability of drugs through the blood-brain barrier (BBB), and drug resistance. To overcome the aforementioned issues in fighting brain cancer, there is an imperative need for designing novel therapeutic approaches. Exosomes have been proposed as prospective "Trojan horse" nanocarriers of anticancer theranostics owing to their biocompatibility, increased stability, permeability, negligible immunogenicity, prolonged circulation time, and high loading capacity. This review provides a comprehensive discussion on the biological properties, physicochemical characteristics, isolation methods, biogenesis and internalization of exosomes, while it emphasizes their therapeutic and diagnostic potential as drug vehicle systems in brain cancer, highlighting recent advances in the research field. A comparison of the biological activity and therapeutic effectiveness of several exosome-encapsulated cargo including drugs and biomacromolecules underlines their great supremacy over the non-exosomal encapsulated cargo in the delivery, accumulation, and biological potency. Various studies on cell lines and animals give prominence to exosome-based nanoparticles (NPs) as a promising and alternative approach in the management of brain cancer.
Despite the recognised contribution of the stroma to breast cancer development and progression, the effective targeting of the tumor microenvironment remains a challenge to be addressed. We ...previously reported that normal fibroblasts (NFs) and, notably, breast cancer-associated fibroblasts (CAFs) induced epithelial-to-mesenchymal transition and increases in cell membrane fluidity and migration in well- (MCF-7) and poorly-differentiated (MDA-MB-231) breast cancer cells. This study was designed to better define the role played, especially by CAFs, in promoting breast tumor cell migration.
Fibroblast/breast cancer cell co-cultures were set up to investigate the influence of NFs and CAFs on gene and protein expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, as well as on the protein level and activity of its transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), in MCF-7 and MDA-MB-231 cells. To assess the role of SREBP1 in the regulation of SCD1 expression, the desaturase levels were also determined in tumor cells treated with an SREBP1 inhibitor. Migration was evaluated by wound-healing assay in SCD1-inhibited (by small-interfering RNA (siRNA) or pharmacologically) cancer cells and the effect of CAF-conditioned medium was also assessed. To define the role of stroma-derived signals in cancer cell migration speed, cell-tracking analysis was performed in the presence of neutralising antibodies to hepatocyte growth factor, transforming growth factor-β or basic fibroblast growth factor.
A two to three fold increase in SCD1 mRNA and protein expression has been induced, particularly by CAFs, in the two cancer cell lines that appear to be dependent on SREBP1 activity in MCF-7 but not in MDA-MB-231 cells. Both siRNA-mediated and pharmacological inhibition of SCD1 impaired tumor cells migration, also when promoted by CAF-released soluble factors. Fibroblast-triggered increase in cancer cell migration speed was markedly reduced or abolished by neutralising the above growth factors.
These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies.
The aim of this investigation was to prepare novel hybrid materials with enhanced antimicrobial properties to be used in food preservation and packaging applications. Therefore, nanocomposite ...materials were synthesized based on two stimuli-responsive oligo(ethylene glycol methacrylate)s, namely PEGMA and PEGMEMA, the first bearing hydroxyl side groups with three different metal nanoparticles, i.e., Ag, TiO2 and ZnO. The in situ radical polymerization technique was employed to ensure good dispersion of the nanoparticles in the polymer matrix. FTIR spectra identified the successful preparation of the corresponding polymers and XRD scans revealed the presence of the nanoparticles in the polymer matrix. In the polymer bearing hydroxyl groups, the presence of Ag-NPs led to slightly lower thermal stability as measured by TGA, whereas both ZnO and TiO2 led to nanomaterials with better thermal stability. The antimicrobial activity of all materials was determined against the Gram-negative bacteria E. coli and the Gram-positive S. aureus, B. subtilis and B. cereus. PEGMEMA nanocomposites had much better antimicrobial activity compared to PEGMA. Ag NPs exhibited the best inhibition of microbial growth in both polymers with all four bacteria. Nanocomposites with TiO2 showed a very good inhibition percentage when used in PEGMEMA-based materials, while in PEGMA material, high antimicrobial activity was observed only against E. coli and B. subtilis, with moderate activity against B. cereus and almost absent activity against S. aureus. The presence of ZnO showed antimicrobial activity only in the case of PEGMEMA-based materials. Differences observed in the antibacterial activity of the polymers with the different nanoparticles could be attributed to the different structure of the polymers and possibly the more efficient release of the NPs.
SARS-CoV-2 ORF3a accessory protein was found to be involved in virus release, immunomodulation and exhibited a pro-apoptotic character. In order to unravel a potential ORF3a-induced apoptotic and ...inflammatory death mechanism, lung epithelial cells (A549) were transfected with in vitro synthesized
mRNA. The protein's dynamic involvement as "stress factor" for the endoplasmic reticulum, causing the activation of PERK kinase and other UPR-involved proteins and therefore the upregulation of their signaling pathway executioners (ATF6, XBP-1s, PERK, phospho eIF2a,
, CHOP,
), has been clearly demonstrated. Furthermore, the overexpression of BAX and BH3-only pro-apoptotic protein PUMA, the upregulation of Bcl-2 family genes (
), the reduced expression of Bcl-2 in mRNA and protein levels, and lastly, the cleavage of PARP-1 and caspase family members (caspase-3,-8 and -9) indicate that ORF3a displays its apoptotic character through the mitochondrial pathway of apoptosis. Moreover, the upregulation of
, phosphorylation of p65 and IκΒα and the elevated expression of pro-inflammatory cytokines (IL-1b, IL-6, IL-8 and IL-18) in transfected cells with
mRNA indicate that this protein causes the inflammatory response through NFκB activation and therefore triggers lung injury. An intriguing finding of our study is that upon treatment of the ORF3a-transfected cells with GSK2606414, a selective PERK inhibitor, both complications (apoptosis and inflammatory response) were neutralized, and cell survival was favored, whereas treatment of transfected cells with z-VAD (a pan-caspase inhibitor) despite inhibiting cell death, could not ameliorate the inflammatory response of transfected A549 cells. Given the above, we point out that PERK kinase is a "master tactician" and its activation constitutes the main stimulus for the emergence of ORF3a apoptotic and inflammatory nature and therefore could serve as potential target for developing novel therapeutic approaches against COVID-19.
This work describes the design, preparation, and deep investigation of "intelligent nanobiomaterials" that fulfill the safety rules and aim to serve as "signal deliverers" for osteogenesis, harboring ...a specific peptide that promotes and enhances osteogenesis at the end of their hydrogel fibers. The de novo synthesized protein fibers, besides their mechanical properties owed to their protein constituents from elastin, silk fibroin and mussel-foot adhesive protein-1 as well as to cell-attachment peptides from extracellular matrix glycoproteins, incorporate the Bone Morphogenetic Protein-2 (BMP2) peptide (AISMLYLDEN) that, according to our studies, serves as "signal deliverer" for osteogenesis. The osteogenetic capacity of the biomaterial has been evidenced by investigating the osteogenic marker genes
,
,
,
,
, and
, which were increased drastically in cells cultured on scaffold-BMP2 for 21 days, even in the absence of osteogenesis medium. In addition, the induction of phosphorylation of intracellular Smad-1/5 and Erk-1/2 proteins clearly supported the osteogenetic capacity of the biomaterial.
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