Real-time monitoring of a 3D blood-brain barrier model maturation and integrity with a sensorized microfluidic device.

A significant challenge in the treatment of central nervous system (CNS) disorders is represented by the presence of the blood-brain barrier (BBB), a highly selective membrane that regulates molecular transport and restricts the passage of pathogens and therapeutic compounds. Traditional models are constrained by high costs, lengthy experimental timelines, ethical concerns, and interspecies variations. models, particularly microfluidic BBB-on-a-chip devices, have been developed to address these limitations.

Polydopamine Nanoparticle-Based Combined Chemotherapy and Photothermal Therapy for the Treatment of Liver Cancer.

Polydopamine nanoparticles (PDA NPs) are proposed as an anti-cancer tool against hepatocellular carcinoma through the combination of near-infrared (NIR)-mediated hyperthermia and loading with a chemotherapeutic drug, sorafenib (SRF). Cell membranes isolated from a liver cancer cell line (HepG2) have been exploited for the coating of the nanoparticles (thus obtaining CM-SRF-PDA NPs), to promote homotypic targeting toward cancer cells. The selective targeting ability and the combined photothermal and chemotherapeutic activity of the CM-SRF-PDA NPs following NIR irradiation have been evaluated on cell cultures in static and dynamic conditions, besides three-dimensional culture models.

Drug-Loaded Polydopamine Nanoparticles for Chemo/Photothermal Therapy against Colorectal Cancer Cells.

Colorectal cancer (CRC) is a common and deadly malignancy, ranking second in terms of mortality and third in terms of incidence on a global scale. The survival rates for CRC patients are unsatisfactory primarily because of the absence of highly effective clinical strategies. The efficacy of existing CRC treatments, such as chemotherapy (CT), is constrained by issues such as drug resistance and damage to healthy tissues.

Nanomaterials as Microglia Modulators in the Treatment of Central Nervous System Disorders.

Microglia play a pivotal role in the central nervous system (CNS) homeostasis, acting as housekeepers and defenders of the surrounding environment. These cells can elicit their functions by shifting into two main phenotypes: pro-inflammatory classical phenotype, M1, and anti-inflammatory alternative phenotype, M2. Despite their pivotal role in CNS homeostasis, microglia phenotypes can influence the development and progression of several CNS disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, ischemic stroke, traumatic brain injuries, and even brain cancer.

Sensorization of microfluidic brain-on-a-chip devices: Towards a new generation of integrated drug screening systems.

Brain-on-a-chip (BoC) devices show typical characteristics of brain complexity, including the presence of different cell types, separation in different compartments, tissue-like three-dimensionality, and inclusion of the extracellular matrix components. Moreover, the incorporation of a vascular system mimicking the blood-brain barrier (BBB) makes BoC particularly attractive, since they can be exploited to test the brain delivery of different drugs and nanoformulations. In this review, we introduce the main innovations in BoC and BBB-on-a-chip models, especially focusing sensorization: electrical, electrochemical, and optical biosensors permit the real-time monitoring of different biological phenomena and markers, such as the release of growth factors, the expression of specific receptors/biomarkers, the activation of immune cells, cell viability, cell-cell interactions, and BBB crossing of drugs and nanoparticles.

Magnetic self-assembly of 3D multicellular microscaffolds: A biomimetic brain tumor-on-a-chip for drug delivery and selectivity testing.

In recent years, the need for highly predictive brain cancer models to test new anticancer compounds and experimental therapeutic approaches has significantly increased. Realistic brain tumor-on-a-chip platforms would allow a more accurate selection of valid candidate drugs and nanomedicines, therefore alleviating the economic and ethical issues of unsuccessful studies . Here, we present a multi-functional self-assembled brain tumor-on-a-chip model characterized by 3D glioma cultures interfaced both to nonmalignant brain cells of the peritumoral niche and to a 3D-real-scale blood-brain barrier (BBB) microfluidic system.

Combining confocal microscopy, dSTORM, and mass spectroscopy to unveil the evolution of the protein corona associated with nanostructured lipid carriers during blood-brain barrier crossing.

Upon coming into contact with the biological environment, nanostructures are immediately covered by biomolecules, particularly by proteins forming the so-called "protein corona" (PC). The phenomenon of PC formation has gained great attention in recent years due to its implication in the use of nanostructures in biomedicine. In fact, it has been shown that the formation of the PC can impact the performance of nanostructures by reducing their stability, causing aggregation, increasing their toxicity, and providing unexpected and undesired nanostructure-cell interactions.

Natural Antioxidant Compounds as Potential Pharmaceutical Tools against Neurodegenerative Diseases.

Natural antioxidants are a very large diversified family of molecules classified by activity (enzymatic or nonenzymatic), chemical-physical properties (e.g., hydrophilic or lipophilic), and chemical structure (e.

study of polydopamine nanoparticles as protective antioxidant agents in fibroblasts derived from ARSACS patients.

Reactive oxygen species (ROS) are active molecules involved in several biological functions. When the production of ROS is not counterbalanced by the action of protective antioxidant mechanisms present in living organisms, a condition of oxidative stress can arise with consequent damage to biological structures. The brain is one of the main ROS-generating organs in the human body, with the consequence that most of the neurological disorders are associated with an overproduction of ROS.

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.

Cerium oxide nanoparticles administration during machine perfusion of discarded human livers: A pilot study.

The combined approach of ex situ normothermic machine perfusion (NMP) and nanotechnology represents a strategy to mitigate ischemia/reperfusion injury in liver transplantation (LT). We evaluated the uptake, distribution, and efficacy of antioxidant cerium oxide nanoparticles (nanoceria) during normothermic perfusion of discarded human livers. A total of 9 discarded human liver grafts were randomized in 2 groups and underwent 4 h of NMP: 5 grafts were treated with nanoceria conjugated with albumin (Alb-NC; 50 µg/ml) and compared with 4 untreated grafts.

Liposomes loaded with polyphenol-rich grape pomace extracts protect from neurodegeneration in a rotenone-based model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease with no satisfactory therapy options. Similar to other neurodegenerative conditions, such as Alzheimer's and Huntington's diseases, oxidative stress plays a key factor in the neurodegeneration process. To counteract the uncontrolled increase of reactive oxygen species (ROS) and oxidative stress-dependent cell death, several preclinical and clinical tests exploit natural-derived organic antioxidants, such as polyphenols.

Cerium Oxide Nanoparticle Administration to Skeletal Muscle Cells under Different Gravity and Radiation Conditions.

For their remarkable biomimetic properties implying strong modulation of the intracellular and extracellular redox state, cerium oxide nanoparticles (also termed "nanoceria") were hypothesized to exert a protective role against oxidative stress associated with the harsh environmental conditions of spaceflight, characterized by microgravity and highly energetic radiations. Nanoparticles were supplied to proliferating C2C12 mouse skeletal muscle cells under different gravity and radiation levels. Biological responses were thus investigated at a transcriptional level by RNA next-generation sequencing.

Delivery of Thyronamines (TAMs) to the Brain: A Preliminary Study.

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1).

ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis.

Background: Metastatic breast cancer is a major cause of cancer-related deaths in woman. Brain metastasis is a common and devastating site of relapse for several breast cancer molecular subtypes, including oestrogen receptor-positive disease, with life expectancy of less than a year. While efforts have been devoted to developing therapeutics for extra-cranial metastasis, drug penetration of blood-brain barrier (BBB) remains a major clinical challenge.

Polydopamine Nanoparticles as an Organic and Biodegradable Multitasking Tool for Neuroprotection and Remote Neuronal Stimulation.

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.

Smart diagnostic nano-agents for cerebral ischemia.

Cerebral ischemia (or ischemic stroke) is undeniably one of the most important life-threatening cerebral disorders. It occurs due to a clot formation in one of the blood arteries supplying the brain, causing a reduction or interruption of the blood flow. To date, the use of thrombolytics like the recombinant tissue plasminogen activator or the use of mechanical thrombectomy are the only two food and drug administration-approved treatments.

Antioxidants and Nanotechnology: Promises and Limits of Potentially Disruptive Approaches in the Treatment of Central Nervous System Diseases.

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.

CeO Nanoparticles-Loaded pH-Responsive Microparticles with Antitumoral Properties as Therapeutic Modulators for Osteosarcoma.

Osteosarcoma is an aggressive form of bone cancer mostly affecting young people. To date, the most effective strategy for the treatment of osteosarcoma is the surgical removal of the tumor with or without combinational chemotherapy. In this study, we present the development of a pH-sensitive drug-delivery system in the form of microparticles, with increased chemotherapeutic action against the osteosarcoma cell line SAOS-2, and with reduced toxicity against the heart myoblastic cell line H9C2.

Cell Membrane-Coated Magnetic Nanocubes with a Homotypic Targeting Ability Increase Intracellular Temperature due to ROS Scavenging and Act as a Versatile Theranostic System for Glioblastoma Multiforme.

In this study, hybrid nanocubes composed of magnetite (Fe O ) and manganese dioxide (MnO ), coated with U-251 MG cell-derived membranes (CM-NCubes) are synthesized. The CM-NCubes demonstrate a concentration-dependent oxygen generation (up to 15%), and, for the first time in the literature, an intracellular increase of temperature (6 °C) due to the exothermic scavenging reaction of hydrogen peroxide (H O ) is showed. Internalization studies demonstrate that the CM-NCubes are internalized much faster and at a higher extent by the homotypic U-251 MG cell line compared to other cerebral cell lines.

Design, Fabrication, and In Vitro Evaluation of Nanoceria-Loaded Nanostructured Lipid Carriers for the Treatment of Neurological Diseases.

Neurodegenerative diseases comprise a large group of disorders characterized by a dramatic synaptic connections loss, occurring as a result of neurodegeneration, which is closely related to the overproduction of reactive oxygen and nitrogen species. Currently, the treatment of neurodegenerative diseases has been limited mainly because of the inability of the synthesized delivery systems to cross the blood-brain barrier and to successfully deliver their therapeutic cargo to the diseased tissue. Taking into consideration the aforementioned limitations, we designed a lipid-based nanotherapeutic vector composed of biomimetic lipids and CeO nanoparticles (nanoceria, NC).

Nutlin-loaded magnetic solid lipid nanoparticles for targeted glioblastoma treatment.

Aim: Glioblastoma multiforme is one of the deadliest forms of cancer, and current treatments are limited to palliative cares. The present study proposes a nanotechnology-based solution able to improve both drug efficacy and its delivery efficiency.

Materials & Methods: Nutlin-3a and superparamagnetic nanoparticles were encapsulated in solid lipid nanoparticles, and the obtained nanovectors (nutlin-loaded magnetic solid lipid nanoparticle [Nut-Mag-SLNs]) were characterized by analyzing both their physicochemical properties and their effects on U-87 MG glioblastoma cells.

Piezoelectric barium titanate nanostimulators for the treatment of glioblastoma multiforme.

Major obstacles to the successful treatment of gliolastoma multiforme are mostly related to the acquired resistance to chemotherapy drugs and, after surgery, to the cancer recurrence in correspondence of residual microscopic foci. As innovative anticancer approach, low-intensity electric stimulation represents a physical treatment able to reduce multidrug resistance of cancer and to induce remarkable anti-proliferative effects by interfering with Ca and K homeostasis and by affecting the organization of the mitotic spindles. However, to preserve healthy cells, it is utterly important to direct the electric stimuli only to malignant cells.