Fast diagnosis and more efficient therapies for cancer surely represent one of the huge tasks for the worldwide researchers’ and clinicians’ community. In the last two decades, our understanding of the biology and molecular pathology of cancer mechanisms, coupled with the continuous development of the material science and technological compounds, have successfully improved nanomedicine applications in oncology. This review argues on nanomedicine application of engineered extracellular vesicles (EVs) in oncology. All the most innovative processes of EVs engineering are discussed together with the related degree of applicability for each one of them in cancer nanomedicines.

Oxidative stress represents a common issue in most neurological diseases, causing severe impairments of neuronal cell physiological activity that ultimately lead to neuron loss of function and cellular death. In this work, lipid-coated polydopamine nanoparticles (L-PDNPs) are proposed both as antioxidant and neuroprotective agents, and as a photothermal conversion platform able to stimulate neuronal activity. L-PDNPs showed the ability to counteract reactive oxygen species (ROS) accumulation in differentiated SH-SY5Y, prevented mitochondrial ROS-induced dysfunctions and stimulated neurite outgrowth. Moreover, for the first time in the literature, the photothermal conversion capacity of L-PDNPs was used to increase the intracellular temperature of neuron-like cells through near-infrared (NIR) laser stimulation, and this phenomenon was thoroughly investigated using a fluorescent temperature-sensitive dye and modeled from a mathematical point of view. It was also demonstrated that the increment in temperature caused by the NIR stimulation of L-PDNPs was able to produce a Ca 2+ influx in differentiated SH-SY5Y, being, to the best of our knowledge, the first example of organic nanostructures used in such an approach. This work could pave the way to new and exciting applications of polydopamine-based and of other NIR-responsive antioxidant nanomaterials in neuronal research.

In the last years, different nanotools have been developed to fight cancer cells. They could be administered alone, exploiting their intrinsic toxicity, or remotely activated to achieve cell death. In the latter case, ultrasound (US) has been recently proposed to stimulate some nanomaterials because of the US outstanding property of deep tissue penetration and the possibility of focusing. In this study, for the first time, we report on the highly efficient killing capability of amino-propyl functionalized ZnO nanocrystals (ZnO NCs) in synergy with high-energy ultrasound shock waves (SW) for the treatment of cancer cells. The cytotoxicity and internalization of ZnO NCs were evaluated in cervical adenocarcinoma KB cells, as well as the safety of the SW treatment alone. Then, the remarkably high cytotoxic combination of ZnO NCs and SW was demonstrated, comparing the effect of multiple (3 times/day) SW treatments toward a single one, highlighting that multiple treatments are necessary to achieve efficient cell death. At last, preliminary tests to understand the mechanism of the observed synergistic effect were carried out, correlating the nanomaterial surface chemistry to the specific type of stimulus used. The obtained results can thus pave the way for a novel nanomedicine treatment, based on the synergistic effect of nanocrystals combined with highly intense mechanical pressure waves, offering high efficiency, deep and focused tissue penetration, and a reduction of side effects on healthy cells.

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-NH 2 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-NH 2 NCs when exposed to pulsed ultrasound. Furthermore, to evaluate the applicability of ZnO-NH 2 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-NH 2 NCs in combination with pulsed ultrasound anticipating their applicability in the fields of biology and health care.

Zinc oxide nanoparticles (ZnO NPs) are currently among the most promising nanomaterials for theranostics. However, they suffer from some drawbacks that could prevent their application in nanomedicine as theranostic agents. The doping of ZnO NPs can be effectively exploited to enhance the already-existing ZnO properties and introduce completely new functionalities in the doped material. Herein, we propose a novel synthetic approach for iron-doped ZnO (Fe:ZnO) NPs as a multifunctional theranostic nanoplatform aimed at cancer cell treatment. Pure ZnO and Fe:ZnO NPs, with two different levels of iron doping, were synthesized by a rapid wet-chemical method and analyzed in terms of morphology, crystal structure and chemical composition. Interestingly, Fe:ZnO NPs featured bioimaging potentialities thanks to superior optical properties and novel magnetic responsiveness. Moreover, iron doping provides a way to enhance the electromechanical behavior of the NPs, which are then expected to show enhanced therapeutic functionalities. Finally, the intrinsic therapeutic potentialities of the NPs were tested in terms of cytotoxicity and cellular uptake with both healthy B lymphocytes and cancerous Burkitt’s lymphoma cells. Furthermore, their biocompatibility was tested with a pancreatic ductal adenocarcinoma cell line (BxPC-3), where the novel properties of the proposed iron-doped ZnO NPs can be potentially exploited for theranostics.