Technologies for Cancer Research

1noopenopenLimongi TaniaLimongi, Tani

Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

The design, synthesis and characterization of new nanomaterials represents one of the most dynamic and transversal aspects of nanotechnology applications in the biomedical field. New synthetic and engineering improvements allow the design of a wide range of biocompatible nanostructured materials (NSMs) and nanoparticles (NPs) which, with or without additional chemical and/or biomolecular surface modifications, are more frequently employed in applications for successful diagnostic, drug delivery and therapeutic procedures. Metal-based nanoparticles (MNPs) including metal NPs, metal oxide NPs, quantum dots (QDs) and magnetic NPs, thanks to their physical and chemical properties have gained much traction for their functional use in biomedicine. In this review it is highlighted how the generation of reactive oxygen species (ROS), which in many respects could be considered a negative aspect of the interaction of MNPs with biological matter, may be a surprising nanotechnology weapon. From the exchange of knowledge between branches such as materials science, nanotechnology, engineering, biochemistry and medicine, researchers and clinicians are setting and standardizing treatments by tuning ROS production to induce cancer or microbial cell death

Progressive Muscle Fatigue Induces Loss in Muscle Force and Persistent Activation of Frontal Cortex as Measured by Multi-Channel fNIRT

The effect of fatiguing skeletal muscle exercise on brain, and in particular on ipsi- and ontralateral frontal cortex (FC) has not been fully clarified. The aim of this study was to investigate by functional near-infrared topography (fNIRT) the FC oxygenation response to a prolonged fatiguing rhythmic handgrip exercise performed at the maximal voluntary contraction separately with right or left hand. fNIRT is a not harmful and non-invasive optical technique allowing the simultaneous acquisition of oxygenated and deoxygenated hemoglobin concentration ([O2Hb], [HHb]) changes on the scalp. By using a 8-channel fNIRT (NIRO-200 with multi-fiber adapter, Hamamatsu Photonics) we demonstrated a significant [O 2Hb] increase, accompanied by a smaller and delayed significant [HHb] decrease, in all measurements points of both hemispheres. A significant hemisphere x task execution modality interaction was revealed only for [O2Hb] increase of the right FC during the right handgrip exercise (p= 0.008). A significant hemisphere x task execution modality interaction was found only for [HHb] decrease of the left FC during the left handgrip exercise (p<0.001). These results provide further evidence that FC plays a role in maintaining strength of the forearm muscles and ensuring a correct execution of motor tasks which require a fine motor control and coordination

Detecting Mental Calculation Related Frontal Cortex Oxygenation Changes for Brain Computer Interface Using Multi-Channel Functional Near Infrared Topography

Multi-channel functional near infrared topography (fNIRT) is a non-harmful, non-invasive and safe optical imaging technique that allows the simultaneous acquisition of oxygenated and deoxygenated hemoglobin concentration changes on the scalp. This study was aimed at investigating the potential use of fNIRT in association with a cognitive system, namely the working memory, for brain-computer interface (BCI). By using a 8-channel fNIRT system (NIRO-200 with multi-fiber adapter, Hamamatsu Photonics), we demonstrated in eight subjects that the mental calculation provokes over the frontal cortical region a significant increase in oxygenated hemoglobin and a concomitant smaller and delayed significant decrease in deoxygenated hemoglobin in all measurements points of both hemispheres. This result indicates that cortical regions involved in higher cognitive functions may serve as a readily self-controllable input for BCI fNIRT based applications

Cytotoxicity and Thermal Characterization Assessment of Excipients for the Development of Innovative Lyophilized Formulations for Oncological Applications

Freeze-drying, also known as lyophilization, significantly improves the storage, stability, shelf life, and clinical translation of biopharmaceuticals. On the downside, this process faces complex challenges, i.e., the presence of freezing and drying stresses for the active compounds, the uniformity and consistency of the final products, and the efficiency and safety of the reconstituted lyophilized formulations. All these requirements can be addressed by adding specific excipients that can protect and stabilize the active ingredient during lyophilization, assisting in the formation of solid structures without interfering with the biological and/or pharmaceutical action of the reconstituted products. However, these excipients, generally considered safe and inert, could play an active role in the formulation interacting with the biological cellular machinery and promoting toxicity. Any side effects should be carefully identified and characterized to better tune any treatments in terms of concentrations and administration times. In this work, various concentrations in the range of 1 to 100 mg/mL of cellobiose, lactose, sucrose, trehalose, isoleucine, glycine, methionine, dextran, mannitol, and (2-hydroxypropyl)-β-cyclodextrin were evaluated in terms of their ability to create uniform and solid lyophilized structures. The freeze-dried products were then reconstituted in the appropriate cell culture media to assess their in vitro cytotoxicity on both a healthy cell line (B-lymphocytes) and their tumoral lymphoid counterpart (Daudi). Results showed that at 10 mg/mL, all the excipients demonstrated suitable lyophilized solid structures and high tolerability by both cell lines, while dextran was the only excipient well-tolerated also up to 100 mg/mL. An interesting result was shown for methionine, which even at 10 mg/mL, selectively affected the viability of the cancerous cell line only, opening future perspectives for antitumoral applications

DEVICE FOR OBTAINING THREE-DIMENSIONAL CELL CULTURES, METHOD FOR THE IMPLEMENTATION THEREOF, AND USE OF SUCH DEVICE

A device for obtaining threedimensional cell cultures comprising: a sub strate (1); a plurality of micro-structures (2) which protrude from the surface of the sub strate (1) and are arranged on such substrate (1) according to a periodical grid so as to make the substrate (1) super hydrophobic. The device is characterised in that the micro-struc tures (2) have side walls at least partially nano-patterned and have projections (14) and recesses (16) alternated with a predetermined distance

Tailoring dry microparticles for pulmonary drug delivery: ultrasonic spray freeze-drying with mannitol and salbutamol sulphate

Spray freeze-drying has emerged as a valid alternative to traditional spray drying to produce therapeutic dry microparticles. In particular, the spherical shape and high porosity of spray freeze-dried microparticles make them suitable for pulmonary drug delivery through dry powder inhalers. However, an appropriate particle size and fine particle fraction are required to guarantee lung deposition. This study used ultrasonic spray freeze-drying to generate dry microparticles composed of mannitol either alone or added with the bronchodilator salbutamol sulphate. The influence of the solid concentration and the feed flow rate on the particle size, morphology, surface area, porosity, and crystallinity was investigated. Growing particle size was observed, increasing the concentration and feed flow rate. Similarly, the addition of the drug led to a larger particle size and surface area. The in vitro simulation of drug deposition highlighted the dependence of the aerodynamic properties on the solid concentration and feed flow rate. Due to the lower density and particle geometric size, the highest fine particle fraction (26%) and smallest mass median aerodynamic diameter (4.4 μm) were reached at the lowest solid concentration and feed flow rate

Improving dispersal of therapeutic nanoparticles in the human body

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The Synergistic Effect of Nanocrystals Combined With Ultrasound in the Generation of Reactive Oxygen Species for Biomedical Applications

Reactive oxygen species (ROS) effects on living cells and tissues is multifaceted and their level or dose can considerably affect cell proliferation and viability. It is therefore necessary understand their role also designing ways able to regulate their amount inside cells, i.e., using engineered nanomaterials with either antioxidant properties or, for cancer therapy applications, capable to induce oxidative stress and cell death, through tunable ROS production. In this paper, we report on the use of single-crystalline zinc oxide (ZnO) round-shaped nanoparticles, yet ZnO nanocrystals (NCs) functionalized with amino-propyl groups (ZnO-NH2 NCs), combined with pulsed ultrasound (US). We show the synergistic effects produced by NC-assisted US which are able to produce different amount of ROS, as a result of inertial cavitation under the pulsed US exposure. Using Passive Cavitation Detection (PCD) and Electron Paramagnetic Resonance (EPR) spectroscopy, we systematically study which are the key parameters, monitoring, and influencing the amount of generated ROS measuring their concentration in water media and comparing all the results with pure water batches. We thus propose a ROS generation mechanism based on the selective application of US to the ZnO nanocrystals in water solutions. Ultrasound B-mode imaging is also applied, proving in respect to pure water, the enhanced ecographic signal generation of the aqueous solution containing ZnO-NH2 NCs when exposed to pulsed ultrasound. Furthermore, to evaluate the applicability of ZnO-NH2 NCs in the biomedical field, the ROS generation is studied by interposing different tissue mimicking materials, like phantoms and ex vivo tissues, between the US transducer and the sample well. As a whole, we clearly proof the enhanced capability to produce ROS and to control their amount when using ZnO-NH2 NCs in combination with pulsed ultrasound anticipating their applicability in the fields of biology and health care