Lipidic Formulations Inspired by COVID Vaccines as Smart Coatings to Enhance Nanoparticle-Based Cancer Therapy

Recent advances in nanomedicine have led to the introduction and subsequent establishment of nanoparticles in cancer treatment and diagnosis. Nonetheless, their application is still hindered by a series of challenges related to their biocompatibility and biodistribution. In this paper, we take inspiration from the recently produced and widely spread COVID vaccines, based on the combinational use of ionizable solid lipid nanoparticles, cholesterol, PEGylated lipids, and neutral lipids able to incorporate mRNA fragments. Here, we focus on the implementation of a lipidic formulation meant to be used as a smart coating of solid-state nanoparticles. The composition of this formulation is finely tuned to ensure efficient and stable shielding of the cargo. The resulting shell is a highly customized tool that enables the possibility of further functionalizations with targeting agents, peptides, antibodies, and fluorescent moieties for future in vitro and in vivo tests and validations. Finally, as a proof of concept, zinc oxide nanoparticles doped with iron and successively coated with this lipidic formulation are tested in a pancreatic cancer cell line, BxPC-3. The results show an astonishing increase in cell viability with respect to the same uncoated nanoparticles. The preliminary results presented here pave the way towards many different therapeutic approaches based on the massive presence of highly biostable and well-tolerated nanoparticles in tumor tissues, such as sonodynamic therapy, photodynamic therapy, hyperthermia, and diagnosis by means of magnetic resonance imaging

Doped zinc oxide nanoparticles: Synthesis, characterization and potential use in nanomedicine

Smart nanoparticles for medical applications have gathered considerable attention due to an improved biocompatibility and multifunctional properties useful in several applications, including advanced drug delivery systems, nanotheranostics and in vivo imaging. Among nanomaterials, zinc oxide nanoparticles (ZnO NPs) were deeply investigated due to their peculiar physical and chemical properties. The large surface to volume ratio, coupled with a reduced size, antimicrobial activity, photocatalytic and semiconducting properties, allowed the use of ZnO NPs as anticancer drugs in new generation physical therapies, nanoantibiotics and osteoinductive agents for bone tissue regeneration. However, ZnO NPs also show a limited stability in biological environments and unpredictable cytotoxic effects thereof. To overcome the abovementioned limitations and further extend the use of ZnO NPs in nanomedicine, doping seems to represent a promising solution. This review covers the main achievements in the use of doped ZnO NPs for nanomedicine applications. Sol-gel, as well as hydrothermal and combustion methods are largely employed to prepare ZnO NPs doped with rare earth and transition metal elements. For both dopant typologies, biomedical applications were demonstrated, such as enhanced antimicrobial activities and contrast imaging properties, along with an improved biocompatibility and stability of the colloidal ZnO NPs in biological media. The obtained results confirm that the doping of ZnO NPs represents a valuable tool to improve the corresponding biomedical properties with respect to the undoped counterpart, and also suggest that a new application of ZnO NPs in nanomedicine can be envisioned

Social robots in cognitive interventions. Advances, problems and perspectives

Social Assistive Robots are being used in therapeutic interventions for elderly people affected by cognitive impairments. The present paper reports our research lines aiming at investigating the role of a social robot in aiding therapists during cognitive stimulation sessions for elders with Mild Cognitive Impairment and Mild Dementia. We review our studies whose results show that social robots have been positively accepted by the seniors in different experiments. Participants were very attentive and involved in the sessions’ tasks and their experience was mainly positive. Our data suggest that this technology can be a valid tool to support psychotherapists in cognitive stimulation interventions emphasizing the need of multidisciplinary approaches combining assessment of behavior and robotics

Biodegradable and drug-eluting inorganic composites based on mesoporous zinc oxide for urinary stent applications

Conventional technologies for ureteral stent fabrication suffer from major inconveniences such as the development of encrustations and bacteria biofilm formation. These drawbacks typically lead to the failure of the device, significant patient discomfort and an additional surgery to remove and replace the stent in the worst cases. This work focuses on the preparation of a new nanocomposite material able to show drug elution properties, biodegradation and eventually potential antibacterial activity. Poly(2-hydroxyethyl methacrylate) or the crosslinked poly(2-hydroxyethyl methacrylate)-co-poly(acrylic acid) hydrogels were prepared by the radical polymerization method and combined with a biodegradable and antibacterial filling agent, i.e., flower-like Zinc Oxide (ZnO) micropowders obtained via the hydrothermal route. The physico-chemical analyses revealed the correct incorporation of ZnO within the hydrogel matrix and its highly mesoporous structure and surface area, ideal for drug incorporation. Two different anti-inflammatory drugs (Ibuprofen and Diclofenac) were loaded within each composite and the release profile was monitored up to two weeks in artificial urine (AU) and even at different pH values in AU to simulate pathological conditions. The addition of mesoporous ZnO micropowders to the hydrogel did not negatively affect the drug loading properties of the hydrogel and it was successfully allowed to mitigate undesirable burst-release effects. Furthermore, the sustained release of the drugs over time was observed at neutral pH, with kinetic constants (k) as low as 0.05 h-1. By exploiting the pH-tunable swelling properties of the hydrogel, an even more sustained release was achieved in acidic and alkaline conditions especially at short release times, with a further reduction of burst effects (k ≈ 0.01-0.02 h-1). The nanocomposite system herein proposed represents a new material formulation for preparing innovative drug eluting stents with intrinsic antibacterial properties

Ultrasound Triggered ZnO-Based Devices for Tunable and Multifaceted Biomedical Applications

Smart materials able to respond to an external stimulus or an environmental condition represent milestone developments in modern medicine. Among them, zinc oxide (ZnO) is a highly intriguing inorganic material with versatile morphologies/shapes and multifunctional properties like piezoelectricity, enhanced reactive oxygen species (ROS) generation, and antimicrobial ones. Here, the fabrication of smart ZnO-based films is shown that can remotely be activated by ultrasound (US). US exposure induces electrical potentials on the fabricated devices that can be exploited to stimulate electrically responsive cells or promote ROS generation for cancer treatment. ZnO microparticles with surface nanostructuring are thus synthesized and processed in the form of a paste to deposit thin films on flexible polymeric supports. ZnO paste formulation and the fabrication procedure of the final device are optimized in terms of uniformity, hydrophilicity, and purity. Graphene oxide and poly(2-hydroxyethyl methacrylate) are also layered onto the ZnO films in order to provide the devices with additional functionalities. ROS generation and electro-mechanical performances upon US stimulation are evaluated for all of the developed devices. Finally, biocompatibility studies are conducted with osteoblast-like cell cultures for possible applications in the contexts of bone tissue engineering/therapy

Nutritional, Functional, and Technological Characterization of a Novel Gluten- and Lactose-Free Yogurt-Style Snack Produced With Selected Lactic Acid Bacteria and Leguminosae Flours

Aiming at meeting consumers’ requirements for healthy foods, dietary needs (vegetarianism, lactose- and gluten-free), as well as the nutrition recommendations of the Health Authorities in terms of protein, fibers and bioactive compounds, the present study proposes a novel yogurt-style snack made with plant-derived ingredients. The biotechnological protocol includes the fermentation of a thermal-treated blend of cereal and legume flours by the selected lactic acid bacteria (LAB) Lactoplantibacillus plantarum DSM33326 and Levilactobacillus brevis DSM33325. The yogurt-style snack was characterized by protein and fiber concentration of 3 and 4%, respectively, and a low-fat content. Compared to the unfermented control, the yogurt-style snack was characterized by a significant higher concentration of free amino acids and lower contents of the antinutritional factors, i.e., phytic acid, condensed tannins, saponins and raffinose (up to 90%) mainly due to the LAB metabolic activity. Hence, an in-vitro protein digestibility of 79% and improvements of all the nutritional indexes related to the quality of the protein fraction (e.g., GABA) were achieved at the end of fermentation. According to the Harvard Medical School recommendations, the novel snack can be potentially classified as low-glycemic index food (53%). Antioxidant properties of the fermented snack were also improved by means of increased the total phenol content and radical scavenging activity. High survival rate of the starter LAB and a commercial probiotic (added to the snack) was found through 30 days storage under refrigerated conditions. The biotechnological protocol to make the novel snack here proposed is suitable for the large-scale application in food industry, giving a platform product with a peculiar and appreciated sensory profile

Production of the polyhydroxyalkanoate PHBV from ricotta cheese exhausted whey by haloferax mediterranei fermentation

In the last decade, the dairy industry underwent a rapid expansion due to the increasing demand of milk-based products, resulting in high quantity of wastewater, i.e., whey and ricotta cheese exhausted whey (RCEW). Although containing high content of nutritional compounds, dairy by-products are still disposed as waste rather being reintroduced in a new production chain, hence leading to environmental and economic issues. This study proposes a new biotechnological approach based on the combination of membrane filtration and fermentation to produce poly-hydroxyalkanoates (PHA), biodegradable bioplastics candidate as an alternative to petroleum-derived plastics. The protocol, exploiting the metabolic capability Haloferax mediterranei to synthesize PHA from RCEW carbon sources, was set up under laboratory and pilot scale conditions. A multi-step fractionation was used to recover a RCEW fraction containing 12.6% (w/v) of lactose, then subjected to an enzymatic treatment aimed at releasing glucose and galactose. Fermentation conditions (culture medium for the microorganism propagation, inoculum size, time, and temperature of incubation) were selected according to the maximization of polymer synthesis, under in-flasks experiments. The PHA production was then tested using a bioreactor system, under stable and monitored pH, temperature, and stirring conditions. The amount of the polymer recovered corresponded to 1.18 g/L. The differential scanning calorimetry (DSC) analysis revealed the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as the polymer synthesized, with a relatively high presence of hydroxyvalerate (HV). Identity and purity of the polymer were confirmed by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) and X-ray photoelectron (XPS) spectroscopy analyses. By combining the fractionation of RCEW, one of the most abundant by-products from the agri-food industry, and the use of the halophile Hfx mediterranei, the production of PHBV with high purity and low crystallinity has successfully been optimized. The process, tested up to pilot scale conditions, may be further implemented (e.g., through fed-batch systems) and used for large-scale production of bioplastics, reducing the economical and environmental issues related the RCEW disposal

Efficient content delivery through fountain coding in opportunistic information-centric networks

Opportunistic networks can increase network capacity, support collaborative downloading of content and offload traffic from a cellular to a cellular-assisted, device-to-device network. They can also support communication and content exchange when the cellular infrastructure is under severe stress and when the network is down or inaccessible. Fountain coding has been considered as espe- cially suitable for lossy networks, providing reliable multicast transport without requiring feedback from receivers. It is also ideal for multi-path and multi- source communication that fits exceptionally well with opportunistic networks. In this paper, we propose a content-centric approach for disseminating con- tent in opportunistic networks efficiently and reliably. Our approach is based on Information-Centric Networking (ICN) and employs fountain coding. When tied together, ICN and fountain coding provide a comprehensive solution that overcomes significant limitations of existing approaches. Extensive network simulations indicate that our approach is viable. Cache hit ratio can be increased by up to five times, while the overall network traffic load is reduced by up to four times compared to content dissemination on top of the standard Named Data Networking architecture

Tex19.1 Promotes Spo11-Dependent Meiotic Recombination in Mouse Spermatocytes

Meiosis relies on the SPO11 endonuclease to generate the recombinogenic DNA double strand breaks (DSBs) required for homologous chromosome synapsis and segregation. The number of meiotic DSBs needs to be sufficient to allow chromosomes to search for and find their homologs, but not excessive to the point of causing genome instability. Here we report that the mammal-specific gene Tex19.1 promotes Spo11-dependent recombination in mouse spermatocytes. We show that the chromosome asynapsis previously reported in Tex19.1-/- spermatocytes is preceded by reduced numbers of recombination foci in leptotene and zygotene. Tex19.1 is required for normal levels of early Spo11-dependent recombination foci during leptotene, but not for upstream events such as MEI4 foci formation or accumulation of H3K4me3 at recombination hotspots. Furthermore, we show that mice carrying mutations in Ubr2, which encodes an E3 ubiquitin ligase that interacts with TEX19.1, phenocopy the Tex19.1-/- recombination defects. These data suggest that Tex19.1 and Ubr2 are required for mouse spermatocytes to accumulate sufficient Spo11-dependent recombination to ensure that the homology search is consistently successful, and reveal a hitherto unknown genetic pathway promoting meiotic recombination in mammals