The manifold roles of zinc oxide nanocrystals in interaction with acoustic waves

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Grasping the past: delay can improve visuomotor performance

“Optic ataxia” is caused by damage to the human posterior parietal cortex (PPC). It disrupts all components of a visually guided prehension movement, not only the transport of the hand toward an object's location [1], but also the in-flight finger movements pretailored to the metric properties of the object [2, 3 and 4]. Like previous cases [4 and 5], our patient (I.G.) was quite unable to open her handgrip appropriately when directly reaching out to pick up objects of different sizes. When first tested, she failed to do this even when she had previewed the target object 5 s earlier. Yet despite this deficit in “real” grasping, we found, counterintuitively, that I.G. showed good grip scaling when “pantomiming” a grasp for an object seen earlier but no longer present. We then found that, after practice, I.G. became able to scale her handgrip when grasping a real target object that she had previewed earlier. By interposing catch trials in which a different object was covertly substituted for the original object during the delay between preview and grasp, we found that I.G. was now using memorized visual information to calibrate her real grasping movements. These results provide new evidence that “off-line” visuomotor guidance can be provided by networks independent of the PPC

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

Improving dispersal of therapeutic nanoparticles in the human body

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Smart Shockwave Responsive Titania-Based Nanoparticles for Cancer Treatment

Nanomedicine is an emerging treatment approach for many cancers, characterized by having high sensitivity and selectivity for tumor cells and minimal toxic effects induced by the conventional chemotherapeutics. In these context, smart nanoparticles (NPs) are getting increasingly relevant in the development of new therapies. NPs with specific chemical composition and/or structure and being stimuli-responsive to magnetic, light or ultrasound waves are new promising tools. In the present work, amorphous-titania propyl-amine functionalized (a-TiO2-NH2) NPs, coated with bovine serum albumin (BSA), are stimulated with high energy shock waves to induce cytotoxic effects in cancer cells. First, a new method to coat a-TiO2-NH2 NPs with BSA (a-TiO2-NH2/BSA) was proposed, allowing for a high dispersion and colloidal stability in a cell culture media. The a-TiO2-NH2/BSA NPs showed no cancer cell cytotoxicity. In a second step, the use of shock waves to stimulate a-TiO2-NH2/BSA NPs, was evaluated and optimized. A systematic study was performed in in vitro cell culture aiming to impair the cancer cell viability: NP concentrations, time steps and single versus multiple shock waves treatments were studied. The obtained results highlighted the relevance of NPs design and administration time point with respect to the shock wave treatment and allow to hypothesize mechanical damages to cells

Artificial and Naturally Derived Phospholipidic Bilayers as Smart Coatings of Solid-State Nanoparticles: Current Works and Perspectives in Cancer Therapy

Recent advances in nanomedicine toward cancer treatment have considered exploiting liposomes and extracellular vesicles as effective cargos to deliver therapeutic agents to tumor cells. Meanwhile, solid-state nanoparticles are continuing to attract interest for their great medical potential thanks to their countless properties and possible applications. However, possible drawbacks arising from the use of nanoparticles in nanomedicine, such as the nonspecific uptake of these materials in healthy organs, their aggregation in biological environments and their possible immunogenicity, must be taken into account. Considering these limitations and the intrinsic capability of phospholipidic bilayers to act as a biocompatible shield, their exploitation for effectively encasing solid-state nanoparticles seems a promising strategy to broaden the frontiers of cancer nanomedicine, also providing the possibility to engineer the lipid bilayers to further enhance the therapeutic potential of such nanotools. This work aims to give a comprehensive overview of the latest developments in the use of artificial liposomes and naturally derived extracellular vesicles for the coating of solid-state nanoparticles for cancer treatment, starting from in vitro works until the up-to-date advances and current limitations of these nanopharmaceutics in clinical applications, passing through in vivo and 3D cultures studies

Biomimetic amorphous titania nanoparticles as ultrasound responding agents to improve cavitation and ros production for sonodynamic therapy

Conventional therapies to treat cancer often exhibit low specificity, reducing the efficiency of the treatment and promoting strong side effects. To overcome these drawbacks, new ways to fight cancer cells have been developed so far focusing on nanosystems. Different action mechanisms to fight cancer cells have been explored using nanomaterials, being their remote activation one of the most promising. Photo-and sonodynamic therapies are relatively new approaches that emerged following this idea. These therapies are based on the ability of specific agents to generate highly cytotoxic reactive oxygen species (ROS) by external stimulation with light or ultrasounds (US), respectively. Crystalline (TiO2) and amorphous titania (a-TiO2) nanoparticles (NPs) present a set of very interesting characteristics, such as their photo-reactivity, photo stability, and effective bactericidal properties. Their production is inexpensive and easily scalable; they are reusable and demonstrated already to be nontoxic. Therefore, these NPs have been increasingly studied as promising photo-or sonosensitizers to be applied in photodynamic/sonodynamic therapies in the future. However, they suffer from poor colloidal stability in aqueous and biological relevant media. Therefore, various organic and polymer-based coatings have been proposed. In this work, the role of a-TiO2 based NPs synthesized through a novel, room-temperature, base-catalyzed, sol-gel protocol in the generation of ROS and as an enhancer of acoustic inertial cavitation was evaluated under ultrasound irradiation. A novel biomimetic coating based on double lipidic bilayer, self-assembled on the a-TiO2-propylamine NPs, is proposed to better stabilize them in water media. The obtained results show that the biomimetic a-TiO2-propylamine NPs are promising candidates to be US responding agents, since an improvement of the cavitation effect occurs in presence of the developed NPs. Further studies will show their efficacy against cancer cells