The Influence of Surface Protein Adsorption on Gold Nanoparticle Intratumoral Distribution and Retention

Nanomedicines’ inability to penetrate throughout the entire volume of a tumor due to heterogeneous distribution within the tumor mass remains a crucial limiting factor for a vast range of theranostic applications, including image-guided radiation therapy. Despite many studies conducted on the topic having shown the efficacy and biocompatibility of colloidal gold nanoparticles (GNPs), the biological effects of GNPs in the tumor microenvironment, including the particle–protein interaction and the consequent impact on cellular pathways and contrast enhancement remain unclear. In this regard, further investigations on how GNP surface passivation affects X-ray attenuation as well as in vivo biodistribution will clarify several aspects still under discussion in the scientific community, which so far have limited the clinical translation of their cancer-related applications. We aim to evaluate the influence of protein surface adsorption on the GNP biodistribution in Lewis lung carcinoma (LLC) tumor-bearing mice using high-resolution computed tomography (CT) pre-clinical imaging. We hypothesize that, by controlling the adsorption of proteins on the GNP surface, we can influence the intratumoral distribution and retention of the particles. GNPs approximately 34 nm in diameter were synthesized with a surface plasmon peak at ~530 nm, surface passivated with bovine serum albumin (BSA) to reduce opsonization and improve colloidal stability, and characterized with standard methods. Modulation of BSA adsorption on the GNPs was observed by tuning the pH of the immobilization medium from acidic to alkaline, which we quantified using Langmuir isotherms. CT phantom imaging was used to determine X-ray attenuation as a function of GNP concentration and surface functionalization. The in vitro study for evaluating the uptake of GNPs by LLC cells highlighted a difference in the internalization depending on the surface functionalization. In both cases, macropinocytosis was the trafficking mechanism, but while endosomes with citrate-GNPs can be found in different stages of maturation, cells treated with BSA-GNPs presented larger vesicles up to 1 μm in diameter. The in vivo study was performed by injecting intratumorally, concentrating GNPs into LLC solid tumors grown on the right flank of 6-week-old female C57BL/6 mice. Ten days post-injection, follow-up assessments with CT imaging showed the distribution and retention of the particles in the tumor. CT attenuation quantification based on bioimaging analysis for each time point was conducted. In vivo results showed significant heterogeneity in the intratumoral biodistribution of GNPs dependent on surface passivation. BSA-GNPs perfused predominately along the tumor periphery with few depositions throughout the entire tumor volume. This response can be explained by the abnormal and heterogeneous vascular structure of the LLC tumor, suggesting perfusion rather than permeability as the limiting factor for tumor accumulation of the GNPs. Despite the perivascular cluster accumulation, the BSA-GNP distribution diverged from that obtained after unpassivated, citrate-GNP intratumoral injections. In conclusion, our investigations have shown that surface passivation of GNPs is able to influence the mechanism of cellular uptake in vitro and their in vivo intratumoral diffusion, highlighting the spatial heterogeneity of the solid tumor

Comparison of Multiple Maximum and Minimum Temperature Datasets at Local Level: The Case Study of North Horr Sub-County, Kenya

Climate analyses at a local scale are an essential tool in the field of sustainable development. The evolution of reanalysis datasets and their greater reliability contribute to overcoming the scarcity of observed data in the southern areas of the world. The purpose of this study is to compute the reference monthly values and ranges of maximum and minimum temperatures for the eight main inhabited villages of North Horr Sub-County, in northern Kenya. The official ten-day dataset derived from the Kenyan Meteorological Department (KMD), the monthly datasets derived from the ERA-Interim reanalysis (ERA), the Observational-Reanalysis Hybrid (ORH) and the Climate Limited Area Mode driven by HadG-EM2-ES (HAD) are assessed on a local scale using the most common statistical indices to determine which is more reliable in representing monthly maximum and minimum temperatures. Overall, ORH datasets showed lower biases and errors in representing local temperatures. Through an innovative methodology, a new set of monthly mean temperature values and ranges derived from ORH datasets are calculated for each location in the study area, in order to guarantee to locals an historical benchmark to compare present observations. The findings of this research provide insights for environmental risk management, supporting local populations in reducing their vulnerability

Procedimento per la generazione e l'analisi di segnali di elettrochemiluminescenza e relativo sistema

La presente invenzione si riferisce a un procedimento per la generazione e l‟analisi di segnali di elettrochemiluminescenza, che comprende le operazioni di generare uno stimolo in una cella elettrochimica comprendente un elettrodo di lavoro comprendente nanotubi di carbonio in contatto con una soluzione da misurare, cui è applicato detto stimolo, e rilevare e analizzare un segnale di elettrochemiluminescenza rappresentativo di radiazione di elettrochemiluminescenza emessa da detta soluzione in risposta a detto stimol

Electrical Impedance-Based Characterization of Hepatic Tissue with Early-Stage Fibrosis

Liver fibrosis is a key pathological precondition for hepatocellular carcinoma in which the severity is confidently correlated with liver cancer. Liver fibrosis, characterized by gradual cell loss and excessive extracellular matrix deposition, can be reverted if detected at the early stage. The gold standard for staging and diagnosis of liver fibrosis is undoubtedly biopsy. However, this technique needs careful sample preparation and expert analysis. In the present work, an ex vivo, minimally destructive, label-free characterization of liver biopsies is presented. Through a custom-made experimental setup, liver biopsies of bile-duct-ligated and sham-operated mice were measured at 8, 15, and 21 days after the procedure. Changes in impedance were observed with the progression of fibrosis, and through data fitting, tissue biopsies were approximated to an equivalent RC circuit model. The model was validated by means of 3D hepatic cell culture measurement, in which the capacitive part of impedance was proportionally associated with cell number and the resistive one was proportionally associated with the extracellular matrix. While the sham-operated samples presented a decrease in resistance with time, the bile-duct-ligated ones exhibited an increase in this parameter with the evolution of fibrosis. Moreover, since the largest difference in resistance between healthy and fibrotic tissue, of around 2 kW, was found at 8 days, this method presents great potential for the study of fibrotic tissue at early stages. Our data point out the great potential of exploiting the proposed needle setup in clinical applications

A “Plant-Wearable System” for Its Health Monitoring by Intra- and Interplant Communication

A step forward in smart agriculture is moving to direct monitoring plants and crops instead of their environment. Understanding plant status is crucial in improving food production and reducing the usage of water and chemicals in agriculture. Here, we propose a “plant-wearable,” low-cost, and low-power method to measure in-vivo green plant stem frequency as the indicator for plant watering stress status. Our method is based on measuring the frequency of a digital signal obtained with a relaxation oscillator where the plant is a part of the feedback loop. The frequency was correlated with the soil water potential, used as a critical indicator of plant water stress, and an 85% correlation was found. In this way, the measuring system matches all the requirements of smart agriculture and Internet of Things (IoT): ultra-low-cost, low-complexity, ultra-low-power, and small sizes, introducing the concept of wearability in plant monitoring. The proposed solution exploits the plant and the soil as a communication channel: the signal carrying the plant watering stress status information is transmitted to a receiving system connected to a different plant. The system's current consumption is lower than 50 μμ A during the transmission in the plant and 40 mA for wireless communication. During inactivity periods, the total current consumption is lower than 15 μμ A. Another important aspect is that the system has to be energy autonomous. Our proposal is based on energy harvesting solutions from multiple sources: solar cells and plant microbial fuel cells. This way, the system is batteryless, thanks to supercapacitors as a storage element. The system can be deployed in the fields and used to monitor plants directly in their environment