Gallium(iii) complexes with polypridyl ligands are shown to kill bulk osteosarcoma cells and osteosarcoma stem cells (OSCs) with up to nanomolar potency.
The delivery of nucleic acids relies on vectors that condense and encapsulate their cargo. Especially nonviral gene delivery systems are of increasing interest. However, low transgene expression levels and limited tolerability of these systems remain a challenge. The improvement of nucleic acid delivery using depolymerized chitosan–polyethylenimine DNA complexes (dCS‐PEI/DNA) is investigated. The secore complexes are further combined with chitosan‐based shells and functionalized with polyethylene glycol (PEG) and cell penetrating peptides. This modular approach allows to evaluate the effect of functional shell components on physicochemical particle characteristics and biological effects. The optimized ternary complex combines a core‐dCS‐linear PEI/DNA complex with a shell consisting of dCS‐PEG‐COOH, which results in improved nucleic acid encapsulation, cellular uptake and transfection potency in human hepatoma HuH‐7cells and murine primary hepatocytes. Effects on transgene expression are confirmed in wild‐type mice following retrograde intrabiliary infusion. After administration of only 100 ng complexed DNA, ternary complexes induced a high reporter gene signal for three days. It is concluded that ternary coreshell structured nanoparticles comprising functionalized chitosan can be used for in vitro andin vivo gene delivery.
Despite their high sensitivity and their suitability for miniaturization, biosensors are still limited for clinical applications due to the lack of reproducibility and specificity of their detection performance. The design and preparation of sensing surfaces are suspected to be a cause of these limitations. Here, we first present an updated overview of the current state of use of capacitive biosensors in a medical context. Then, we summarize the encountered strategies for the fabrication of capacitive biosensing surfaces. Finally, we describe the characteristics which govern the performance of the sensing surfaces, along with recent developments that were suggested to overcome their main current limitations.
The COVID-19 pandemic has highlighted the necessity to develop fast, highly sensitive and selective virus detection methods. Surface-based DNA-biosensors are interesting candidates for this purpose. Functionalization of solid substrates with DNA must be precisely controlled to achieve the required accuracy and sensitivity. In particular, achieving high hybridization density at the sensing surface is a prerequisite to reach a low limit of detection. We herein describe a strategy based on peptides as anchoring units to immobilize DNA probes at the surface of borosilicate slides. While the coating pathway involves copper-catalyzed click chemistry, a copper-free variation is also reported. The resulting biochips display a high hybridization density (2.9 pmol per cm2) with their targeted gene sequences.
Surface-based biosensors have proven to be of particular interest in the monitoring of human pathogens by means of their distinct nucleic acid sequences. Genosensors rely on targeted gene/DNA probe hybridization at the surface of a physical transducer and have been exploited for their high specificity and physicochemical stability. Unfortunately, these sensing materials still face limitations impeding their use in current diagnostic techniques. Most of their shortcomings arise from their suboptimal surface properties, including low hybridization density, inadequate probe orientation, and biofouling. Herein, we describe and compare two functionalization methodologies to immobilize DNA probes on a glass substrate via a thermoresponsive polymer in order to produce genosensors with improved properties. The first methodology relies on the use of a silanization step, followed by PET-RAFT of NIPAM monomers on the coated surface, while the second relies on vinyl sulfone modifications of the substrate, to which the pre-synthetized PNIPAM was grafted to. The functionalized substrates were fully characterized by means of X-ray photoelectron spectroscopy for their surface atomic content, fluorescence assay for their DNA hybridization density, and water contact angle measurements for their thermoresponsive behavior. The antifouling properties were evaluated by fluorescence microscopy. Both immobilization methodologies hold the potential to be applied to the engineering of DNA biosensors with a variety of polymers and other metal oxide surfaces.
29 April 2024 in Journal of Science Policy & Governance
The “Science and Policy - How to Bridge the Gap” summer school, which took place in July 2023 in Switzerland, aimed to educate PhD students in natural science and engineering on engaging with policymakers effectively. Over the course of five days, the program covered various aspects of the Swiss and international science-policy interface, including the Science for Policy framework, concrete examples of evidence-based policy advice from scientists, and talks on the significance of Open Science (OS) and public engagement in fostering the dialogue between science and society. Additionally, multiple workshops illustrated science communication formats for different audiences, such as policymakers, stakeholders, and the general public. Organized by five PhD students with a natural science and/or engineering background, the event brought together thirty participants and featured twenty-eight speakers, creating a highly international and stimulating learning environment. This workshop review, written by the summer school organizers, summarizes the school’s outcomes and aims to provide valuable insights for early-career scientists and engineers taking their first steps in science-informed policymaking. The roles scientists may play at the science-policy interface, the various meeting points (physical and ideological) to interact with decision-makers, tools for more effective communication with non-expert audiences, and the importance of OS and Citizen Science (CS) in integrating scientific information more widely into society are discussed. Based on the participants’ feedback, suggestions are also offered for future events on science and policy, which early-career researchers can implement in their respective universities and countries. Given the strong commitment of participants and their desire to create a community, the authors believe such workshops are essential to give early-career scientists the tools and network to actively engage in the science-policy landscape.