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.

Cancer accounts for millions of deaths every year and, due to the increase and aging of the world population, the number of new diagnosed cases is continuously rising. Although many progresses in early diagnosis and innovative therapeutic protocols have been already set in clinical practice, still a lot of critical aspects need to be addressed in order to efficiently treat cancer and to reduce several drawbacks caused by conventional therapies. Nanomedicine has emerged as a very promising approach to support both early diagnosis and effective therapy of tumors, and a plethora of different inorganic and organic multifunctional nanomaterials have been ad hoc designed to meet the constant demand for new solutions in cancer treatment. Given their unique features and extreme versatility, nanocarriers represent an innovative and easily adaptable tool both for imaging and targeted therapy purposes, in order to improve the specific delivery of drugs administered to cancer patients. The current review reports an in-depth analysis of the most recent research studies aiming at developing both inorganic and organic materials for nanomedical applications in cancer diagnosis and therapy. A detailed overview of different approaches currently undergoing clinical trials or already approved in clinical practice is provided.

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.

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Many central nervous system (CNS) diseases are still incurable and only symptomatic treatments are available. Oxidative stress is suggested to be a common hallmark, being able to cause and exacerbate the neuronal cell dysfunctions at the basis of these pathologies, such as mitochondrial impairments, accumulation of misfolded proteins, cell membrane damages, and apoptosis induction. Several antioxidant compounds are tested as potential countermeasures for CNS disorders, but their efficacy is often hindered by the loss of antioxidant properties due to enzymatic degradation, low bioavailability, poor water solubility, and insufficient blood–brain barrier crossing efficiency. To overcome the limitations of antioxidant molecules, exploitation of nanostructures, either for their delivery or with inherent antioxidant properties, is proposed. In this review, after a brief discussion concerning the role of the blood–brain barrier in the CNS and the involvement of oxidative stress in some neurodegenerative diseases, the most interesting research concerning the use of nano‐antioxidants is introduced and discussed, focusing on the synthesis procedures, functionalization strategies, in vitro and in vivo tests, and on recent clinical trials.

The modeling of the pathological microenvironment of the central nervous system (CNS) represents a disrupting approach for drug screening for advanced therapies against tumors and neuronal disorders. The in vitro investigations of the crossing and diffusion of drugs through the blood–brain barrier (BBB) are still not completely reliable, due to technological limits in the replication of 3D microstructures that can faithfully mimic the in vivo scenario. Here, an innovative 1:1 scale 3D-printed realistic biohybrid model of the brain tumor microenvironment, with both luminal and parenchyma compartments, is presented. The dynamically controllable microfluidic device, fabricated through two-photon lithography, enables the triple co-culture of hCMEC/D3 cells, forming the internal biohybrid endothelium of the capillaries, of astrocytes, and of magnetically-driven spheroids of U87 glioblastoma cells. Tumor spheroids are obtained from culturing glioblas-toma cells inside 3D microcages loaded with superparamagnetic iron oxide nanoparticles (SPIONs). The system proves to be capable in hindering dextran diffusion through the bioinspired BBB, while allowing chemotherapy-loaded nanocarriers to cross it. The proper formation of the selective barrier and the good performance of the anti-tumor treatment demonstrate that the proposed device can be successfully exploited as a realistic in vitro model for high-throughput drug screening in CNS diseases.

Glioblastoma multiforme (GBM), also known as grade IV astrocytoma, represents the most aggressive primary brain tumor. The complex genetic heterogeneity, the acquired drug resistance, and the presence of the blood-brain barrier (BBB) limit the efficacy of the current therapies, with effectiveness demonstrated only in a small subset of patients. To overcome these issues, here we propose an anticancer approach based on ultrasound-responsive drug-loaded organic piezoelectric nanoparticles. This anticancer nanoplatform consists of nutlin-3a-loaded ApoE-functionalized P(VDF-TrFE) nanoparticles, that can be remotely activated with ultrasound-based mechanical stimulations to induce drug release and to locally deliver anticancer electric cues. The combination of chemotherapy treatment with chronic piezoelectric stimulation resulted in activation of cell apoptosis and anti-proliferation pathways, induction of cell necrosis, inhibition of cancer migration, and reduction of cell invasiveness in drug-resistant GBM cells. Obtained results pave the way for the use of innovative multifunctional nanomaterials in less invasive and more focused anticancer treatments, able to reduce drug resistance in GBM.

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.