Innovative approaches for cancer treatment: current perspectives and new challenges

Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate critical side effects caused by conventional treatments. Different technologies are currently under evaluation in clinical trials or have been already introduced into clinical practice. While nanomedicine is contributing to the development of biocompatible materials both for diagnostic and therapeutic purposes, bioengineering of extracellular vesicles and cells derived from patients has allowed designing ad hoc systems and univocal targeting strategies. In this review, we will provide an in-depth analysis of the most innovative advances in basic and applied cancer research

Optimization of Humanoid Robot Designs for Human-Robot Ergonomic Payload Lifting

When a human and a humanoid robot collaborate physically, ergonomics is a key factor to consider. Assuming a given humanoid robot, several control architectures exist nowadays to address ergonomic physical human-robot collaboration. This paper takes one step further by considering robot hardware parameters as optimization variables in the problem of collaborative payload lifting. The variables that parametrize robot's kinematics and dynamics ensure their physical consistency, and the human model is considered in the optimization problem. By leveraging the proposed modelling framework, the ergonomy of the interaction is maximized, here given by the agents' energy expenditure. Robot kinematic, dynamics, hardware constraints and human geometries are considered when solving the associated optimization problem. The proposed methodology is used to identify optimum hardware parameters for the design of the ergoCub robot, a humanoid possessing a degree of embodied intelligence for ergonomic interaction with humans. For the optimization problem, the starting point is the iCub humanoid robot. The obtained robot design reaches loads at heights in the range of 0.8-1.5 m with respect to the iCub robot whose range is limited to 0.8-1.2 m. The robot energy expenditure is decreased by about 33%, meanwhile, the human ergonomy is preserved, leading overall to an improved interaction.Comment: Accepted to 2022 IEEE-RAS International Conference on Humanoid Robotics (Humanoids

Modulation of anti-angiogenic activity using ultrasound-activated nutlin-loaded piezoelectric nanovectors

Angiogenesis plays a fundamental role in tumor development, as it is crucial for tumor progression, metastasis development, and invasion. In this view, anti-angiogenic therapy has received considerable attention in several cancer types in order to inhibit tumor vascularization, and the progress of nanotechnology offers opportunities to target and release anti-angiogenic agents in specific diseased areas. In this work, we showed that the angiogenic behavior of human cerebral microvascular endothelial cells can be inhibited by using nutlin-3a-loaded ApoE-functionalized polymeric piezoelectric nanoparticles, which can remotely respond to ultrasound stimulation. The anti-angiogenic effect, derived from the use of chemotherapy and chronic piezoelectric stimulation, leads to disruption of tubular vessel formation, decreased cell migration and invasion, and inhibition of angiogenic growth factors in the presence of migratory cues released by the tumor cells. Overall, the proposed use of remotely activated piezoelectric nanoparticles could provide a promising approach to hinder tumor-induced angiogenesis

Superparamagnetic iron oxide nanoparticles for magnetic hyperthermia: recent advancements, molecular effects, and future directions in the omics era.

Coating and targeting strategies improve superparamagnetic iron oxide nanoparticles-induced hyperthermia, while omics can unveil molecular effects

Characterization and stability of catanionic vesicles formed by pseudo-tetraalkyl surfactant mixtures

The phase behavior of an ad hoc synthesized surfactant, sodium 8-hexadecylsulfate (8-SHS), and its mixtures with didecyldimethylammonium bromide (DiDAB) in water is reported. We dealt with dilute concentration regimes, at a total surfactant content of <30 mmol kg-1 where vesicular aggregates may be formed. The high synergistic behavior of such catanionic mixtures is concomitant with strongly negative interaction parameters, β (≈-18 kBT), significant gain in the free energy of association, ΔGagg, and much lower association concentration compared to the pure surfactants. Vesicle size and ζ-potential depend on the mixture composition. Hydrodynamic diameters increase by progressive addition of oppositely charged surfactants to the one in excess. Counter-intuitively, the ζ-potential becomes more negative at DiDAB molar fractions close to 0.2. The same holds in the reverse case, the ζ-potential becomes more positive after small additions of 8-SHS; anyhow, the effect is more significant in anionic-rich mixtures. This phenomenon was explained by assuming a significant release of counterions and an asymmetric distribution of the two surfactants in the inner and outer vesicle leaflets. The equimolar mixtures form a cubic phase rather than the expected lamellar one. The effect of NaBr concentration on the stability of catanionic vesicles was also investigated. At high NaBr concentrations, all systems are destabilized. For DiDAB-rich vesicles, flocculation is observed, while for 8-SHS-rich ones, lamellar domains are formed at the bottom of the samples. The role played by NaBr depends on whether it is added before or after mixing the surfactants. In particular, preformed catanionic vesicles show a great kinetic stability towards addition of NaBr compared to those obtained by other procedures.We thank Jaume Caelles, in the SAXS-WAXS service at IQAC, for X-Ray measurements; Imma Carrera for technical assistance in the synthesis and surface tension measurements. Financial support from MINECO CTQ2013-41514-P and MAT2012- 38047-CO-02 is gratefully acknowledged. Financial support from Generalitat de Catalunya 2014SGR836 is gratefully acknowledged. Financial support from “La Sapienza” University of Rome (IT) is acknowledged too.Peer reviewe

Hybrid Magnetic Nanovectors Promote Selective Glioblastoma Cell Death through a Combined Effect of Lysosomal Membrane Permeabilization and Chemotherapy

Glioblastoma multiforme is the most aggressive brain tumor, due to its high invasiveness and genetic heterogeneity. Moreover, the blood-brain barrier prevents many drugs from reaching a therapeutic concentration at the tumor site, and most of the chemotherapeutics lack in specificity toward cancer cells, accumulating in both healthy and diseased tissues, with severe side effects. Here, we present in vitro investigations on lipid-based nanovectors encapsulating a drug, nutlin-3a, and superparamagnetic iron oxide nanoparticles, to combine the proapoptotic action of the drug and the hyperthermia mediated by superparamagnetic iron oxide nanoparticles stimulated with an alternating magnetic field. The nanovectors are functionalized with the peptide angiopep-2 to induce receptor-mediated transcytosis through the blood-brain barrier and to target a receptor overexpressed by glioma cells. The glioblastoma multiforme targeting efficiency and the blood-brain barrier crossing abilities were tested through in vitro fluidic models, where different human cell lines were placed to mimic the tumor microenvironment. These nanovectors successfully cross the blood-brain barrier model, maintaining their targeting abilities for glioblastoma multiforme with minimal interaction with healthy cells. Moreover, we showed that nanovector-assisted hyperthermia induces a lysosomal membrane permeabilization that not only initiates a caspase-dependent apoptotic pathway, but also enhances the anticancer efficacy of the drug

Tannic Acid-Iron Complex-Based Nanoparticles as a Novel Tool against Oxidative Stress

: Accumulation of reactive oxygen species in cells leads to oxidative stress, with consequent damage for cellular components and activation of cell-death mechanisms. Oxidative stress is often associated with age-related conditions, as well as with several neurodegenerative diseases. For this reason, antioxidant molecules have attracted a lot of attention, especially those derived from natural sources─like polyphenols and tannins. The main issue related to the use of antioxidants is their inherent tendency to be oxidized, their quick enzymatic degradation in biological fluids, and their poor bioavailability. Nanomedicine, in this sense, has helped in finding new solutions to deliver and protect antioxidants; however, the concentration of the encapsulated molecule in conventional nanosystems could be very low and, therefore, less effective. We propose to exploit the properties of tannic acid, a known plant-derived antioxidant, to chelate iron ions, forming hydrophobic complexes that can be coated with a biocompatible and biodegradable phospholipid to improve stability in biological media. By combining nanoprecipitation and hot sonication procedures, we obtained three-dimensional networks composed of tannic acid-iron with a hydrodynamic diameter of ≈200 nm. These nanostructures show antioxidant properties and scavenging activity in cells after induction of an acute chemical pro-oxidant insult; moreover, they also demonstrated to counteract damage induced by oxidative stress both in vitro and on an in vivo model organism (planarians)