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This dataset contains expert assessments of the cybersecurity skills required for six job profiles in Europe, as determined via surveys responded by cybersecurity experts from academia and industry. The data can be used to identify educational needs in the cybersecurity sector and compare against other frameworks. The six cybersecurity-oriented job profiles used in the surveys are: General cybersec auditor; Technical cybersec auditor; Threat modelling engineer; Security engineer; Enterprise cybersecurity practitioner; Cybersecurity analyst. Data—i.e. expert assessments—was collected via surveys, targeted at European experts in cybersecurity from academia and industry. Respondents characterised the skills needed to perform in six job profiles using the CSEC+ framework: a cybersecurity skills framework prepared as a spreadsheet where cybersecurity skills must be ranked in a Likert scale from 0 (irrelevant) to 4 (advance knowledge needed). Metadata requested included the type of organisation of the respondent (Large company, SME, Academic/Research, Public administration, Other) and the country of origin. There were three data-collection phases: (1) an initial phase, used also to refine later larger-scale processes, carried out in Oct 2021–Jan 2022 and resulting in 13 expert assessments from four EU countries; (2) a second phase implemented as an online service broadcast to a larger audience, carried out in Mar–Apr 2022 and resulting in 15 assessments from eight European countries; (3) and a third phase, allowing direct online input and distributed in PC and mobile form, carried out in Sep–Oct 2022 and resulting in 32 assessments from ten European countries. The raw data gathered was stored and processed via spreadsheets, computing statistical information (mean, stdev) on how much each cybersecurity skill and area was deemed necessary to perform in each job profile. This is visualised as a heatmap where colour intensity symbolises value, and circle diffusion symbolises spread. Processed data further includes visualisations on how the area of origin of the respondent (academia, as in “producer of education”, vs. industry, as in “consumer of education”) influences the responses. This is shown as bar plots, where whiskers represent confidence intervals used for statistical-significance tests. This data can serve as basis to understand the educational needs for the cybersecurity sector in Europe. It can be reused for comparison against frameworks, other than CSEC+, to assess the need of education in specific cybersecurity sectors such as human security. Furthermore, the Qualtrics survey template (included) is a ready-made solution for replication studies.

In the digitalized world, there is a growing need not only to improve one’s cybersecurity skills and knowledge, but also to find ways to optimize the learning process, for example by motivating the learners or optimising the learning facilities, material and the learners for the process. Cyber exercises ran within cyber ranges/arenas (CR) are an efficient way for the exercise participants to improve their cybersecurity skills and knowledge level. The pedagogical way of orienteering the participant to a learning situation is to have a preliminary survey, which prepares the participant for the upcoming event, adds self-reflection, and may even provide feedback and background information for the educator about the upcoming event. The objective of the survey is to improve the quality of the exercise by knowing the interest areas, preferences and other useful information about the participants that is then be used optimise the exercise accordingly. This study analyses the structure of one preliminary survey targeted for the cyber exercise event to be held in January 2022. The questions are justified according to existing frameworks. We have collected a set of structured questions presenting different topics related to the participants’ professional background and expectations towards the exercise. In addition to the short-term goal of analysing the survey for one cyber exercise, this work benefits the long-term goal for improving the skills of cybersecurity professionals. Our further work will validate the results of our preliminary analysis and analyse its correspondence with the survey results, and the final analysis constructed after the cyber exercise.

To address the issue of educating and training new experts in cybersecurity, it is crucial to identify the specific educational needs of the various professions that exist in the field. We measure these needs by analysing six cybersecurity-related job profiles—each with its own specific skill requirements—that have been assessed by academic and industrial organisations from the cybersecurity community in 14 European countries. We find that it is possible to identify a series of “transversal” skills relevant to all job profiles, and thus of utmost importance in the cybersecurity curricula. However, we also observe that academic and industrial priorities differ substantially, and that skills related to the area of Human security do not rank particularly high, possibly exposing the difficulty of integrating such concepts in traditional education.

Future factories will contain a huge number of interconnected systems and various Internet of Things (IoT) devices. Due to the increased complexity, the identity and access management of these systems during their entire device life cycle is a challenging task. At the same time, there is a shift from legacy automation protocols to the use of Internet protocols. This development isincreasing connectivity that will also expose more subsystems to new kinds of attacks. This article presents the typical device life cycle requirements for identity and access management in future industrial automation context also known as the factory of the future (FoF). We have considered two architecture candidates, namely the cloud and web-based architectures. The requirementsfor a device life cycle management system called PROSE are given as an example use case. The article describes our research by presenting a practical example of the requirements that have been used to build a device life cycle management system.

Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/β-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/β-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.

Digital transformation of the manufacturing sector is proceeding rapidly and means a drastic change especially to large companies that drive the development. Manufacturing SMEs are also required to invest in modern technologies to keep up with the competition, as they are often members of supply chains led by large companies. We present a snapshot of the current SME digital investments based on the findings of a study carried out recently as part of our H2020 project covering most of Europe. The questions we aim to answer are: what are the areas of operation where digital solutions have been implemented in, what digital applications have been implemented, what have been the initial barriers faced in the adoption of digital solutions, and what kind of risks SMEs have considered regarding their digital investments. The article provides insights for experts working in digital development for the manufacturing sector and focused on SMEs.

Tumor Therapy A pH-responsive cluster metal–organic framework nanoparticle is developed by Wenguo Cui, Baiyong Shen, Hélder A. Santos, and co-workers in article number 2203915, based on acid-induced conversion from hydrophilicity to hydrophobicity, leading to aggregated nanoparticles. These nanoparticles inhibit tumor growth and reactivate the tumor microenvironment in both pancreatic and breast cancer models.

Modern complex cyber-physical systems heavily rely on humans and AI for mission-critical operations and decision making. Unfortunately, these components are often 'black boxes' to the operator, either because the decision models are too complex for human comprehension (e.g. deep neural networks) or are intentionally hidden (e.g. proprietary intellectual property). In these cases, the decision logic cannot be validated and therefore trust is forced.

Porous silicon (PSi) nanoparticles have been applied in various fields, such as catalysis, imaging, and biomedical applications, because of their large specific surface area, easily modifiable surface chemistry, biocompatibility, and biodegradability. For biomedical applications, it is important to precisely control the surface modification of PSi-based materials and quantify the functionalization density, which determines the nanoparticle’s behavior in the biological system. Therefore, we propose here an optimized solution to quantify the functionalization groups on PSi, based on the nuclear magnetic resonance (NMR) method by combining the hydrolysis with standard 1H NMR experiments. We optimized the hydrolysis conditions to degrade the PSi, providing mobility to the molecules for NMR detection. The NMR parameters were also optimized by relaxation delay and the number of scans to provide reliable NMR spectra. With an internal standard, we quantitatively analyzed the surficial amine groups and their sequential modification of polyethylene glycol. Our investigation provides a reliable, fast, and straightforward method in quantitative analysis of the surficial modification characterization of PSi requiring a small amount of sample.

As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, the metal-organic framework nanoparticles have inadequate accumulation in the tumor tissues, limiting the therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly (ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nano-shell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLNL. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLNL, increasing their uptake in cancer cells and accumulation in the tumor. ZIF@SLNL nanoparticle induced reactive oxygen species (ROS). Ap released from Ap-ZIF@SLNL significantly promoted intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLNL inhibited tumor growth, increased the survival rate in mice, activated the tumor microenvironment, and improved the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLNTL. Furthermore, mice showed normal physiological responses of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects. This article is protected by copyright. All rights reserved

Critical system resilience is a focus point in risk management due to the severe consequences of system failure. As such critical systems become increasingly cyber-physical, cybersecurity vulnerabilities also play a more significant role in system analysis. Now, as the world turns to Artificial Intelligence (AI)-based solutions, the novel vulnerabilities in AI and other black box components add a complexity dimension to the assessment of cyber-physical critical system analysis. This chapter provides a closer look at a Model Based Systems Engineering (MBSE) approach to assess and design the resilience of complex systems throughout their life cycle. As a case study of a system of systems comprised of Unmanned Aerial Systems (UASs) and Unmanned Surface Vessels (USVs) for littoral zone patrol is presented with a focus on system resilience under a national security mission.

Porous silicon (PSi) is a biocompatible and biodegradable material, which can be utilized in biomedical applications. It has several favorable properties, which makes it an excellent material for building engineered nanosystems for drug delivery and diagnostic purposes. One significant hurdle for commercial applications of PSi is the lack of industrial scale production of nanosized PSi particles. Here, we report a novel two-step production method for PSi nanoparticles. The method is based on centrifuge chemical vapor deposition (cCVD) of elemental silicon in an industrial scale reactor followed by electrochemical post-processing to porous particles. Physical properties, biocompatibility and in vivo biodistribution of the cCVD produced nanoparticles were investigated and compared to PSi nanoparticles conventionally produced from silicon wafers by pulse electrochemical etching. Our results demonstrate that the cCVD production provides PSi nanoparticles with comparable physical and biological quality to the conventional method. This method may circumvent several limitations of the conventional method such as the requirements for high purity monocrystalline silicon substrates as starting material and the material losses during the top-down milling process of the pulse-etched films to porous nanoparticles. However, the electroless etching required for the porosification of cCVD-produced nanoparticles limited control over the pore size, but is amenable for scaling of the production to industrial requirements.

Industrial slag containing Si, Al, Ca, Fe, Mg and Ti was used as source for synthesis of novel catalytic materials upon variation of the treating agents (sodium hydroxide, ethylenediaminetetraacetic acid disodium salt dihydrate - sodium hydroxide and tetraethylammonium hydroxide - sodium hydroxide mixtures) and synthesis parameters (solution concentration, synthesis temperature and time). Physico-chemical properties of the raw slag and the catalysts were evaluated by nitrogen physisorption, scanning electron microscopy, energy dispersive X-ray analysis, temperature programmed desorption of CO2 and NH3, transmission electron microscopy, and X-ray powder diffraction. Catalytic activity of the most promising slag-based material was investigated in analytical pyrolysis of wood biomass. Synthesized materials exhibited highly crystalline phases of CaCO3, Ca(OH)2, Ca2SiO4, SiO2, Al2O3, Fe2O3,and TiO2 and showed high basicity due to the presence of large amounts of basic components. Treatment with surfactants had a significant influence on formation of acid sites. Modification of slag textural properties and internal porous structure by such treatment resulted in formation of pores and channels depending on the leaching agent. Upon variation of a leaching agent the specific surface area of the raw slag could be changed from 19 m2/g up to 80 m2/g, what turned out to be important in creation of an effective catalyst for biomass pyrolysis. Slag treatment improved its catalytic activity, which was evidenced by variations of the liquid yield and composition of pinewood derived compounds in non-catalytic and catalytic pyrolysis using original slag and the catalysis synthesized on its basis.

Introduction: Porous silicon (PSi) nanoparticles are capable of delivering therapeutic payloads providing targeted delivery and sustained release of the payloads. In this work we describe the development and proof-of-concept in vivo evaluation of thermally hydrocarbonized porous silicon (PSi) nanoparticles that are implanted with radioactive $^{155}$Tb atoms and coated with red blood cell (RBC) membrane ($^{155}$Tb-THCPSi). The developed nanocomposites can be utilized as an intravenous delivery platform for theranostic radionuclides. Methods: THCPSi thin films were implanted with $^{155}$Dy ions that decay to 155Tb at the ISOLDE radioactive ion-beam (RIB) facility at CERN. The films were processed to nanoparticles by ball-milling and sonication, and subsequently coated with either a solid lipid and RBC membrane or solely with RBC membrane. The nanocomposites were evaluated in vitro for stability and in vivo for circulation half-life and ex vivo for biodistribution in Balb/c mice. Results: Nanoporous THCPSi films were successfully implanted with $^{155}$Tb and processed to coated nanoparticles. The in vitro stability of the particles in plasma and buffer solutions was not significantly different between the particle types, and therefore the RBC membrane coated particles with less laborious processing method were chosen for the biological evaluation. The RBC membrane coating enhanced significantly the blood halflife compared to bare THCPSi particles. In the ex vivo biodistribution study a pronounced accumulation to the spleen was found, with lower uptake in the liver and a minor uptake in the lung, gall bladder and bone marrow. Conclusions: We have demonstrated, using $^{155}$Tb RIB-implanted PSi nanoparticles coated with mouse RBC membranes, the feasibility of using such a theranostic nanosystem for the delivery of RIB based radionuclides with prolonged circulation time. Advances in knowledge and implications for patient care: For the first time, the RIB implantation technique has been utilized to produce PSi nanoparticle with a surface modified for better persistence in circulation. When optimized, these particles could be used in targeted radionuclide therapy with a combination of chemotherapeutic payload within the PSi structure.

Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, long circulation time, and capability to transport cargo all around the body, thus presenting enormous potential in medical applications. In this study, we investigated hybrid nanoparticles consisting of nano-sized autologous or allogeneic red blood cell (RBC) membranes encapsulating porous silicon nanoparticles (PSi NPs). These NPs were functionalized with a model cancer antigen TRP2, which was either expressed on the surface of the RBCs by a cell membrane-mimickingblockcopolymer polydimethylsiloxane-b-poly-2-methyl-2-oxazoline, or attached on the PSi NPs, thus hidden within the encapsulation. When in the presence of peripheral blood immune cells, these NPs resulted in apoptotic cell death of T cells, where the NPs having TRP2 within the encapsulation led to a stronger T cell deletion. The deletion of the T cells did not change the relative proportion of CD4+and cytotoxic CD8+T cells. Overall, this work shows the combination of nano-sized RBCs, PSi, and antigenic peptides may have use in the treatment of autoimmune diseases. A. R. acknowledges financial support from the Finnish Cultural Foundation. H. A. S. acknowledges financial support from the University of Helsinki Research Funds, the Sigrid Juselius Foundation, the HiLIFE Research Funds, the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013; Grant No. 310892) and European Research Council Proof-of-Concept Grant (Decision No. 825020). The authors acknowledge the following core facilities funded by Biocenter Finland: Electron Microscopy Unit of the University of Helsinki for providing the facilities for TEM imaging and the Flow Cytometry Unit for providing the facilities for FACS experiments, and Nanomicroscopy Center of Aalto University for providing the facilities for the cryo-TEM imaging. A. R. acknowledges ¿nancial support from the Finnish Cultural Foundation. H. A. S. acknowledges ¿nancial support from the University of Helsinki Research Funds, the Sigrid Juselius Foundation, the HiLIFE Research Funds, the European Research Council under the European Union's Seventh Frame-work Programme (FP/2007–2013; Grant No. 310892) and European Research Council Proof-of-Concept Grant (Decision No. 825020). The authors acknowledge the following core facilities funded by Biocenter Finland: Electron Microscopy Unit of the University of Helsinki for providing the facilities for TEM imaging and the Flow Cytometry Unit for providing the facilities for FACS experiments, and Nanomicroscopy Center of Aalto University for providing the facilities for the cryo-TEM imaging.

Smart grids are evolving towards intelligent electricity grid where the operation of systems is distributed and automatised. Technical solutions to achieve these future needs are proposed using blockchain with smart contracts in many studies, where smart contracts enhance automation. Fundamentally smart contracts will increase security because of their distributed nature and since it inherits the security of blockchain. However, smart contracts are software components, which have special features like the unstoppable nature of applications and may use special languages like Solidity. Our aim in this paper is to get a holistic review in the smart contract life cycle, what potential new vulnerabilities and threats will they introduce and how can they be prevented, and what smart contract specific issues programmers should focus on. We also propose a future direction to achieve more secure smart contracts in smart energy systems.

Cyber ranges are often used to enhance the cybersecurity posture of a company by training relevant skills. These environments are traditionally used to host exercises that simulate cybersecurity scenarios, improve the cybersecurity skills of employees and enhance the security of networks and processes. By using digital twins, it is possible to organise more targeted cyber range trainings to companies operating in the critical infrastructure sector. Especially in this sector it is important to consider the cybersecurity of these environments themselves as they often may handle companyspecific confidential information. This study presents several cybersecurity related threats and challenges that cyber ranges may face during different phases of use. Cyber threats may be exposed to the actual systems that the ranges are meant to protect if these issues are not taken into consideration and mitigated. Malicious attackers may use the information in the cyber ranges to learn the weaknesses in the actual system. We approach the subject by reviewing the relevant literature, which is currently very limited specially when looking at the cybersecurity issues of cyber ranges. We divide the subject into the different phases of cyber range development and use, and also discuss relevant cloud security issues. Finally, we present actions to mitigate the identified cybersecurity threats and issues in cyber ranges when using them for training and awareness activities.

Cyber ranges are often used to enhance the cybersecurity posture of a company by training relevant skills. These environments are traditionally used to host exercises that simulate cybersecurity scenarios, improve the cybersecurity skills of employees and enhance the security of networks and processes. By using digital twins, it is possible to organise cyber range trainings also to the critical infrastructure sector. However, in the aforementioned sector it is important to consider the cybersecurity of these environments themselves as they often may handle company-specific confidential information. This study presents several cybersecurity related threats and challenges that cyber ranges may face during different phases of use. Cyber threats may be exposed to the actual systems that the ranges are meant to protect if these issues are not taken into consideration and mitigated. Malicious attackers may use the information inthe cyber range to learn the weaknesses in the actual system. We approach the subject by reviewing the relevant literature, which is currently very limited especially when looking at the cybersecurity issues of cyber ranges. We divide the subject into the different phases of cyber range development and use, and also discuss relevant cloud security issues. Finally, we present actions to mitigate the identified cybersecurity threats and issues in cyber ranges when using them for training and awareness activities.

Nutrients stimulate the secretion of glucagon-like peptide-1 (GLP-1), an incretin hormone, secreted from enteroendocrine L-cells which decreases food intake. Thus, GLP-1 analogs are approved for the treatment of obesity, yet cost and side effects limit their use. L-cells are mainly localized in the distal ileum and colon, which hinders the utilization of nutrients targeting GLP-1 secretion. This study proposes a controlled delivery system for nutrients, inducing a prolonged endogenous GLP-1 release which results in a decrease food intake.α-Linolenic acid (αLA) was loaded into thermally hydrocarbonized porous silicon (THCPSi) particles. In vitro characterization and in vivo effects of αLA loaded particles on GLP-1 secretion and food intake were studied in mice. A total of 40.4 ± 3.2% of loaded αLA is released from particles into biorelevant buffer over 24 h, and αLA loaded THCPSi significantly increased in vitro GLP-1 secretion. Single-dose orally given αLA loaded mesoporous particles increased plasma active GLP-1 levels at 3 and 4 h and significantly reduced the area under the curve of 24 h food intake in mice.αLA loaded THCPSi particles could be used to endogenously stimulate sustain gastrointestinal hormone release and reduce food intake.

Porous silicon (PSi) nanoparticles have been applied in various fields, such as catalysis, imaging, and biomedical applications, because of their large specific surface area, easily modifiable surface chemistry, biocompatibility, and biodegradability. For biomedical applications, it is important to precisely control the surface modification of PSi-based materials and quantify the functionalization density, which determines the nanoparticle's behavior in the biological system. Therefore, we propose here an optimized solution to quantify the functionalization groups on PSi, based on the nuclear magnetic resonance (NMR) method by combining the hydrolysis with standard

Digitalization has increased the significance of cybersecurity within the current highly interconnected society. The number and complexity of different cyber-attacks as well as other malicious activities has increased during the last decade and affected the efforts needed to maintain a sufficient level of cyber resilience in organisations. Due to Industry 4.0 and the advanced use of IT and OT technologies and the adaptation of IoT devices, sensors, AI technology, etc., cybersecurity can no longer considered to be taken lightly when trying to gain a competitive advantage in business. When transferring from traditional reactive cybersecurity measures to proactive cyber resilience, cyber ranges are considered a particularly useful tool for keeping the organisation in the game. With their background in defence research (e.g., DARPA NCP in 2008), cyber ranges are defined as interactive simulated platforms representing networks, systems, tools, and/or applications in a safe, legal environment that can be used for developing cyber skills or testing products and services. Cyber ranges can be considered vital in facilitating and fostering cybersecurity training, certification, and general education. Despite the definition, cyber ranges seem to be only used by military or so-called “technical people” when quite a few more organisations could benefit from them. This article attempts to reveal the secrets behind cyber ranges and their use focusing on suitable target environments, common functions, and use cases. Our main objective is to identify a classification of cyber ranges and skills related to these diverse types of ranges. We emphasise the cyber resilience of any type of organisation that demands the use of cyber range type of training. Different training scenarios improve different sets of organisational skills. The article is based on an extensive survey on cyber ranges, their use, and technical capabilities that was conducted in CyberSec4Europe project.

Hierarchically nanostructured silicon was produced by regenerative electroless etching (ReEtching) of Si powder made from pulverized anodized porous silicon. This material is characterized by ∼15 nm mesopores, into the walls of which tortuous 2-4 nm pores have been introduced. The walls are sufficiently narrow that they support quantum-confined crystallites that are photoluminescent. With suitable parameters, the ReEtching process also provides control over the emission color of the photoluminescence. Ball milling and hydrosilylation of this powder with undecylenic acid produces nanoparticles with hydrodynamic diameter of ∼220 nm that exhibit robust and bright luminescence that can be excited with either one ultraviolet/visible photon or two near-infrared photons. The long-lived, robust visible photoluminescence of these chemically passivated porous silicon nanoparticles is well-suited for bioimaging and theranostic applications.

[Image: see text] Recent approaches in the treatment of cancer focus on involving the immune system to control the tumor growth. The administration of immunotherapies, like checkpoint inhibitors, has shown impressive results in the long term survival of patients. Cancer vaccines are being investigated as further tools to prime tumor-specific immunity. Biomaterials show potential as adjuvants in the formulation of vaccines, and biomimetic elements derived from the membrane of tumor cells may widen the range of antigens contained in the vaccine. Here, we show how mice presenting an aggressive melanoma tumor model treated twice with the complete nanovaccine formulation showed control on the tumor progression, while in a less aggressive model, the animals showed remission and control on the tumor progression, with a modification in the immunological profile of the tumor microenvironment. We also prove that co-administration of the nanovaccine together with a checkpoint inhibitor increases the efficacy of the treatment (87.5% of the animals responding, with 2 remissions) compared to the checkpoint inhibitor alone in the B16.OVA model. Our platform thereby shows potential applications as a cancer nanovaccine in combination with the standard clinical care treatment for melanoma cancers.

Mesoporous silicon (PSi) is biocompatible and tailorable material with high potential in drug delivery applications. Here, we report of an evaluation of PSi as a carrier platform for theranostics by delivering a radioactive ion beam- (RIB-) based radioactive lanthanoid into tumors in a mouse model of prostate carcinoma. Thermally hydrocarbonized porous silicon (THCPSi) wafers were implanted with 159Dy at the facility for radioactive ion beams ISOLDE located at CERN, and the resulting [159Dy]THCPSi was postprocessed into particles. The particles were intratumorally injected into mice bearing prostate cancer xenografts. The stability of the particles was studied in vivo, followed by ex vivo biodistribution and autoradiographic studies. We showed that the process of producing radionuclide-implanted PSi particles is feasible and that the [159Dy]THCPSi particles stay stable and local inside the tumor over seven days. Upon release of 159Dy from the particles, the main site of accumulation is in the skeleton, which is in agreement with previous studies on the biodistribution of dysprosium. We conclude that THCPSi particles are a suitable platform together with RIB-based radiolanthanoids for theranostic purposes as they are retained after administration inside the tumor and the radiolanthanoid remains embedded in the THCPSi.

Here, an oxidation/acid dual-responsive nanohybrids/ark system was produced. The microfluidics-produced nanohybrids endow the system with an orchestrated cascade from wound detection, reactive oxygen species scavenging, drug release to hydrogel formation. The drug release behavior imitates the dynamic wound healing process, thus rendering an enhanced bio-mimetic regeneration.

Many drugs with anticancer potential fail in their translation to the clinics due to problems related to pharmacokinetics. LEM2 is a new dual inhibitor of MDM2/mutp53-TAp73 interactions with interesting in vitro anticancer activity, which opens new hopes as an unconventional anticancer therapeutic strategy against cancers lacking p53 or with impaired p53 pathways. As others xanthone derivatives, LEM2 has limited aqueous solubility, posing problems to pursue in vivo assays, and therefore limiting its potential clinical translation. In this work, a mesopomus silicon (PSi)-based nanodelivery system was developed with folate functionalization (APTES-TCPSi-PEG-FA) for targeted delivery, which successfully increased LEM2 solubility when compared to bulk LEM2, evidenced in payload release study. Such effect was reflected on the increase of LEM2 cytotoxicity in HCT116 and MDA-MB-231 cancer cells when treated with LEM2-loaded APTES-TCPSi-PEG-FA, by reducing cell viability lower than 50% in comparison with bulk LEM2. Despite the reduced LEM2 loading degree, which still limits its application in further in vivo assays, the results obtained herein recognize PSi-based nanodelivery systems as a promising strategy to improve LEM2 anticancer activity and bioavailability, which will be relevant for the potential use of this potent TAp73 activator in anticancer therapy.

Summary Communication between biological components is critical for homeostasis maintenance among the convergence of complicated bio-signals. For therapeutic nanoparticles (NPs), the general lack of effective communication mechanisms with the external cellular environment causes loss of homeostasis, resulting in deprived autonomy, severe macrophage-mediated clearance, and limited tumor accumulation. Here, we develop a multistage signal-interactive system on porous silicon particles through integrating the Self-peptide and Tyr-Ile-Gly-Ser-Arg (YIGSR) peptide into a hierarchical chimeric signaling interface with “don’t eat me” and “eat me” signals. This biochemical transceiver can act as both the signal receiver for amantadine to achieve NP transformation and signal conversion as well as the signal source to present different signals sequentially by reversible self-mimicking. Compared with the non-interactive controls, these signal-interactive NPs loaded with AS1411 and tanespimycin (17-AAG) as anticancer drugs improve tumor targeting 2.8-fold and tumor suppression 6.5-fold and showed only 51% accumulation in the liver with restricted hepatic injury., Graphical abstract, Highlights • Constructing a signal-interactive NP system improves NP-cell communication efficiency • Functional chimeric peptide design enables orderly integrating of multiple signal modules • Signal-interactive NPs reduce liver accumulation and promote tumor targeting, Zhang et al. report a strategy to construct drug delivery NPs with a multistage signal-interactive mechanism to improve the NP-cell communication efficiency. They show that the system can process signals with a “presenting-receiving-responding-presenting” pattern to enhance homeostasis of NPs in the biological environment, resulting in reduced NP clearance by the immune system, enhanced tumor targeting, and enhanced tumor suspension efficacy.

In this study, the antibacterial efficacy of NO-releasing porous silicon nanoparticles (pSiNPs) is reported. NO-releasing pSiNPs were produced via the conjugation of S-nitrosothiol (SNO) and S-nitrosoglutathione (GSNO) donors to the nanoparticle surfaces. The release of the conjugated NO caused by the decomposition of the conjugated SNO and GSNO was boosted in the presence of ascorbic acid. The released NO was bactericidal to Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), and eliminated bacterial growth within 2 h of incubation without compromising the viability of mammalian cells. These results demonstrate the advantages of NO-releasing pSiNPs for antibacterial applications, for example, in chronic wound treatment. Refereed/Peer-reviewed

openaire: EC/H2020/788489/EU//BioELCell Heart tissue engineering is critical in the treatment of myocardial infarction, which may benefit from drug-releasing smart materials. In this study, we load a small molecule (3i-1000) in new biodegradable and conductive patches for application in infarcted myocardium. The composite patches consist of a biocompatible elastomer, poly(glycerol sebacate) (PGS), coupled with collagen type I, used to promote cell attachment. In addition, polypyrrole is incorporated because of its electrical conductivity and to induce cell signaling. Results from the in vitro experiments indicate a high density of cardiac myoblast cells attached on the patches, which stay viable for at least 1 month. The degradation of the patches does not show any cytotoxic effect, while 3i-1000 delivery induces cell proliferation. Conductive patches show high blood wettability and drug release, correlating with the rate of degradation of the PGS matrix. Together with the electrical conductivity and elongation characteristics, the developed biomaterial fits the mechanical, conductive, and biological demands required for cardiac treatment.

Generation of new neurons by utilizing the regenerative potential of adult neural stem cells (NSCs) and neuroblasts is an emerging therapeutic strategy to treat various neurodegenerative diseases, including neuronal loss after stroke. Committed to neuronal lineages, neuroblasts are differentiated from NSCs and have a lower proliferation rate. In stroke the proliferation of the neuroblasts in the neurogenic areas is increased, but the limiting factor for regeneration is the poor survival of migrating neuroblasts. Survival of neuroblasts can be promoted by small molecules; however, new drug delivery methods are needed to specifically target these cells. Herein, to achieve specific targeting, we have engineered biofunctionalized porous silicon nanoparticles (PSi NPs) conjugated with a specific antibody against polysialylated neural cell adhesion molecule (PSA-NCAM). The PSi NPs loaded with a small molecule drug, SC-79, were able to increase the activity of the Akt signaling pathway in doublecortin positive neuroblasts both in cultured cells and in vivo in the rat brain. This study opens up new possibilities to target drug effects to migrating neuroblasts and facilitate differentiation, maturation and survival of developing neurons. The conjugated PSi NPs are a novel tool for future studies to develop new therapeutic strategies aiming at regenerating functional neurocircuitry after stoke.

Electrostatic charging of powders and powder mixtures were measured on-line during surface adhesion by sliding the powders in a pipe. The cumulative charge was monitored as a function of transferred powder mass. The effect of adhesion on the charging was assessed by observing the slope of the measured curve at the very beginning of the measurement. Due to adhesion, the charging decreased exponentially. For mixtures, the powder with higher concentration initially dominated the charging. The sign of the charge changed as the additive powder started to adhere, indicating that contacts between the two dissimilar powders started to govern the charging.

Effective electrical resistivities and static relative permittivities of binary powder mixtures were measured and compared to theoretical equations given by Generalized Mixture Rule (GMR). The measured values for mixtures were influenced by the resistivity and permittivity of the pure component materials, the particle sizes and by the sticking between the different particles. According to the Random Model (RM), the effective resistivity and relative permittivity of any randomly packed mixture material can be calculated from the component resistivities and relative permittivities, respectively, and their concentrations. It was shown that RM gave good predictions for both quantities for powders if the particle sizes of the component materials were almost the same. However, this was not the case when large NaCl particles were mixed with fine sugar particles. When these mixtures were prepared, finer, more numerous sugar particles coated the larger NaCl particles, and the mixtures were not random but closer to the series configuration. Effect of particle size was studied briefly by mixing very fine NaCl particles with sugar of similar size. With these mixtures, results predicted by RM were obtained.