A New Blend of Litsea cubeba, Pinus mugo, and Cymbopogon winterianus Essential Oil Active as an Anti-tyrosinase Ingredient in Topical Formulations.

Tyrosinase is a target enzyme to be inhibited in order to reduce excessive melanin production and prevent typical age-related skin disorders. Essential oils are complex mixtures of volatile compounds, belonging mainly to monoterpenoids and sesquiterpenoids, which have been relatively little studied as tyrosinase inhibitors. Among the monoterpenoids, citral (a mixture of neral and geranial) is a fragrance compound in several essential oils that has shown interesting tyrosinase inhibitory activity. Although citral is listed as an allergen among the 26 fragrances in Annex III of the Cosmetics Directive 2003/15/EC, it can be safely used for the formulation of topical products in amounts that are not expected to cause skin sensitization, as shown by various commercially available products.The aim of this work was to evaluate two different formulations (oil/water emulsion, oily solution) containing a new combination of essential oils (Litsea cubeba, Pinus mugo, Cymbopogon winterianus) applied to the skin both in nonocclusive and partially occlusive modes. The blend is designed to reduce the concentration of citral to avoid potential skin reactions while taking advantage of the inhibitory activity of citral. Specifically, the amount of citral and other bioactive compounds (myrcene, citronellal) delivered through the skin was studied as a function of formulation and mode of application.The results show that an oil/water emulsion is preferable because it releases the bioactive compounds rapidly and minimizes their evaporative loss. In addition, semi-occluded conditions are required to prevent evaporation, resulting in higher availability of the bioactive compounds in viable skin.

Iron Overload in Brain: Transport Mismatches, Microbleeding Events, and How Nanochelating Therapies May Counteract Their Effects.

Iron overload in many brain regions is a common feature of aging and most neurodegenerative diseases. In this review, the causes, mechanisms, mathematical models, and possible therapies are summarized. Indeed, physiological and pathological conditions can be investigated using compartmental models mimicking iron trafficking across the blood-brain barrier and the Cerebrospinal Fluid-Brain exchange membranes located in the choroid plexus. In silico models can investigate the alteration of iron homeostasis and simulate iron concentration in the brain environment, as well as the effects of intracerebral iron chelation, determining potential doses and timing to recover the physiological state. Novel formulations of non-toxic nanovectors with chelating capacity are already tested in organotypic brain models and could be available to move from in silico to in vivo experiments.

Enhancing Heart Transplantation: Utilizing Gas-Loaded Nanocarriers to Mitigate Cold/Hypoxia Stress.

Gas-loaded nanocarriers (G-LN) show promise in improving heart transplantation (HTx) outcomes. Given their success in reducing cell death during normothermic hypoxia/reoxygenation (H/R) in vitro, we tested their integration into cardioplegic solutions and static cold storage (SCS) during simulated HTx. Wistar rat hearts underwent four hours of SCS with four G-LN variants: O2- or N2-cyclic-nigerosyl-nigerose-nanomonomers (CNN), and O2- or N2-cyclic-nigerosyl-nigerose-nanosponges (CNN-NS). We monitored physiological-hemodynamic parameters and molecular markers during reperfusion to assess cell damage/protection. Hearts treated with nanomonomers (N2-CNN or O2-CNN) showed improvements in left ventricular developed pressure (LVDP) and a trend towards faster recovery of the rate pressure product (RPP) compared to controls. However, nanosponges (N2-CNN-NS or O2-CNN-NS) did not show similar improvements. None of the groups exhibited an increase in diastolic left ventricular pressure (contracture index) during reperfusion. Redox markers and apoptosis/autophagy pathways indicated an increase in Beclin 1 for O2-CNN and in p22phox for N2-CNN, suggesting alterations in autophagy and the redox environment during late reperfusion, which might explain the gradual decline in heart performance. The study highlights the potential of nanomonomers to improve early cardiac performance and mitigate cold/H/R-induced stunning in HTx. These early improvements suggest a promising avenue for increasing HTx success. Nevertheless, further research and optimization are needed before clinical application.

Enhancing Vitamin D3 Efficacy: Insights from Complexation with Cyclodextrin Nanosponges and Its Impact on Gut-Brain Axes in Physiology and IBS Syndrome.

Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (ßNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut-brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut-brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.

Developing Iron Nanochelating Agents: Preliminary Investigation of Effectiveness and Safety for Central Nervous System Applications.

Excessive iron levels are believed to contribute to the development of neurodegenerative disorders by promoting oxidative stress and harmful protein clustering. Novel chelation treatments that can effectively remove excess iron while minimizing negative effects on the nervous system are being explored. This study focuses on the creation and evaluation of innovative nanobubble (NB) formulations, shelled with various polymers such as glycol-chitosan (GC) and glycol-chitosan conjugated with deferoxamine (DFO), to enhance their ability to bind iron. Various methods were used to evaluate their physical and chemical properties, chelation capacity in diverse iron solutions and impact on reactive oxygen species (ROS). Notably, the GC-DFO NBs demonstrated the ability to decrease amyloid-ß protein misfolding caused by iron. To assess potential toxicity, in vitro cytotoxicity testing was conducted using organotypic brain cultures from the substantia nigra, revealing no adverse effects at appropriate concentrations. Additionally, the impact of NBs on spontaneous electrical signaling in hippocampal neurons was examined. Our findings suggest a novel nanochelation approach utilizing DFO-conjugated NBs for the removal of excess iron in cerebral regions, potentially preventing neurotoxic effects.

The Difficulties in Emotion Regulation Scale-Dyadic version: A new tool for the evaluation of the dyadic dysregulation in couple relationships.

A new measure for assessing an individual's perception of the dyadic difficulties in emotion regulation with a romantic partner is tested. The Difficulties in Emotion Regulation Scale-Dyadic (DERS-D) was obtained by adapting some items of the previous Difficulties in Emotion Regulation Scale (DERS) to the dyadic context. The scale was administered both to a sample of university students (N = 835) to explore its factorial structure and to a convenience sample (N = 833) together with the DERS, the DERS-Positive, the Emotion Beliefs Questionnaire (EBQ), and the Emotion Regulation Questionnaire (ERQ) to confirm the factorial structure and to explore its construct validity. Results highlight that DERS-D measures two distinct features, namely the lack of dyadic awareness and the lack of dyadic clarity, and that configural invariance across genders was met. DERS-D subscales' internal consistency was high. The correlations between the DERS-D and the other measures demonstrated its construct and criterion validity. The promising nature of these results is discussed in light of the potential clinical and empirical uses of the DERS-D.

Ultrasonic Preparation of Nano-CaCO3 Templates and Hollow Mesoporous SiO2 Nanoparticles for Voriconazole Loading.

CaCO3 nanoparticles (nano-CaCO3) as nano-templates were prepared using CaCl2 and Na2CO3 solutions under controlled sonication (19.5 kHz). Using the same ultrasonic device, subsequently, hollow mesoporous silica nanoparticles (HMSNs) were obtained by the hard template of nano-CaCO3. HMSNs were selected as carriers for the antifungal drug voriconazole (VOR) loading to overcome poor water solubility. Three-dimensional CaCO3 nanosheets HMSNs were obtained under gentle sonication. Three-dimensional CaCO3 nanosheets of 24.5 nm (hydrodynamic diameter) were obtained under 17.6 W for 3 min. HMSNs were synthesized by double-template method with nano-CaCO3 as the hard template. Transmission electron microscopy measurements showed that the prepared HMSNs possess hollow structures with particle size between 110 and 120 nm. Nitrogen physisorption at -196 °C revealed that the HMSNs had high surface area (401.57 m2/g), high pore volume (0.11 cm3/g), and uniform pore size (2.22 nm) that facilitated the effective encapsulation of VOR in the HMSNs. The loading capacity of VOR (wt%) on the HMSNs was 7.96%, and the total VOR release amount of VOR-HMSNs material was 71.40% at 480 min. The kinetic model confirmed that the release mechanism of HMSNs nanoparticles followed Fickian diffusion at pH = 7.4 and 37 °C. Moreover, the cumulative VOR release at 42 °C (86.05%) was higher than that at 37 °C (71.40%). The cumulative release amount of VOR from the VOR-HMSNs material was 92.37% at pH = 5.8 at the same temperature. Both nano-CaCO3 templates and HMSNs were prepared by sonication at 19.5 kHz. The as-prepared HMSNs can effectively encapsulate VOR and released drug by Fickian diffusion.

Plasminogen activator-coated nanobubbles targeting cellbound ß2-glycoprotein I as a novel thrombus-specific thrombolytic strategy.

ß2-glycoprotein I (ß2-GPI) is a serum protein widely recognized as the main target of antibodies present in patients with antiphospholipid syndrome (APS). ß2-GPI binds to activated endothelial cells, platelets and leukocytes, key players in thrombus formation. We developed a new targeted thrombolytic agent consisting of nanobubbles (NB) coated with recombinant tissue plasminogen activator (rtPA) and a recombinant antibody specific for cell-bound ß2-GPI. The therapeutic efficacy of targeted NB was evaluated in vitro, using platelet-rich blood clots, and in vivo in three different animal models: i) thrombosis developed in a rat model of APS; ii) ferric chloride-induced mesenteric thrombosis in rats, and iii) thrombotic microangiopathy in a mouse model of atypical hemolytic uremic syndrome (C3-gain-of-function mice). Targeted NB bound preferentially to platelets and leukocytes within thrombi and to endothelial cells through ß2-GPI expressed on activated cells. In vitro, rtPA-targeted NB (rtPA-tNB) induced greater lysis of platelet-rich blood clots than untargeted NB. In a rat model of APS, administration of rtPA-tNB caused rapid dissolution of thrombi and, unlike soluble rtPA that induced transient thrombolysis, prevented new thrombus formation. In a rat model of ferric chloride triggered thrombosis, rtPA-tNB, but not untargeted NB and free rtPA, induced rapid and persistent recanalization of occluded vessels. Finally, treatment of C3-gain-of-function mice with rtPA-tNB, that target ß2-GPI deposited in kidney glomeruli, decreased fibrin deposition, and improved urinalysis data with a greater efficiency than untargeted NB. Our findings suggest that targeting cell-bound ß2-GPI may represent an efficient and thrombus-specific thrombolytic strategy in both APS-related and APS-unrelated thrombotic conditions.

Oxygen Nanocarriers for Improving Cardioplegic Solution Performance: Physico-Chemical Characterization.

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure.

Developing New Cyclodextrin-Based Nanosponges Complexes to Improve Vitamin D Absorption in an In Vitro Study.

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, ßNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The ßNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.

Encapsulation in Oxygen-Loaded Nanobubbles Enhances the Antimicrobial Effectiveness of Photoactivated Curcumin.

In both healthcare and agriculture, antibiotic resistance is an alarming issue. Biocompatible and biodegradable ingredients (e.g., curcumin) are given priority in "green" criteria supported by the Next Generation EU platform. The solubility and stability of curcumin would be significantly improved if it were enclosed in nanobubbles (NB), and photoactivation with the correct wavelength of light can increase its antibacterial efficacy. A continuous release of curcumin over a prolonged period was provided by using innovative chitosan-shelled carriers, i.e., curcumin-containing nanobubbles (Curc-CS-NBs) and oxygen-loaded curcumin-containing nanobubbles (Curc-Oxy-CS-NBs). The results demonstrated that after photoactivation, both types of NBs exhibited increased effectiveness. For Staphylococcus aureus, the minimum inhibitory concentration (MIC) for Curc-CS-NBs remained at 46 µg/mL following photodynamic activation, whereas it drastically dropped to 12 µg/mL for Curc-Oxy-CS-NBs. Enterococcus faecalis shows a decreased MIC for Curc-CS-NB and Curc-Oxy-CS-NB (23 and 46 µg/mL, respectively). All bacterial strains were more effectively killed by NBs that had both oxygen and LED irradiation. A combination of Curc-Oxy-CS-NB and photodynamic stimulation led to a killing of microorganisms due to ROS-induced bacterial membrane leakage. This approach was particularly effective against Escherichia coli. In conclusion, this work shows that Curc-CS-NBs and Curc-Oxy-CS-exhibit extremely powerful antibacterial properties and represent a potential strategy to prevent antibiotic resistance and encourage the use of eco-friendly substitutes in agriculture and healthcare.

Design, Characterization, and Biological Activities of Erythromycin-Loaded Nanodroplets to Counteract Infected Chronic Wounds Due to Streptococcus pyogenes.

Streptococcus pyogenes causes a wide spectrum of diseases varying from mild to life threatening, despite antibiotic treatment. Nanoparticle application could facilitate the foreign pathogen fight by increasing the antimicrobial effectiveness and reducing their adverse effects. Here, we designed and produced erythromycin-loaded chitosan nanodroplets (Ery-NDs), both oxygen-free and oxygen-loaded. All ND formulations were characterized for physico-chemical parameters, drug release kinetics, and tested for biocompatibility with human keratinocytes and for their antibacterial properties or interactions with S. pyogenes. All tested NDs possessed spherical shape, small average diameter, and positive Z potential. A prolonged Ery release kinetic from Ery-NDs was demonstrated, as well as a favorable biocompatibility on human keratinocytes. Confocal microscopy images showed ND uptake and internalization by S. pyogenes starting from 3 h of incubation up to 24 h. According to cell counts, NDs displayed long-term antimicrobial efficacy against streptococci significantly counteracting their proliferation up to 24 h, thanks to the known chitosan antimicrobial properties. Intriguingly, Ery-NDs were generally more effective (104-103 log10 CFU/mL), than free-erythromycin (105 log10 CFU/mL), in the direct killing of streptococci, probably due to Ery-NDs adsorption by bacteria and prolonged release kinetics of erythromycin inside S. pyogenes cells. Based on these findings, NDs and proper Ery-NDs appear to be the most promising and skin-friendly approaches for the topical treatment of streptococcal skin infections allowing wound healing during hypoxia.

Exploitation of the Antibacterial Properties of Photoactivated Curcumin as 'Green' Tool for Food Preservation.

In the search for non-chemical and green methods to counteract the bacterial contamination of foods, the use of natural substances with antimicrobial properties and light irradiation at proper light waves has been extensively investigated. In particular, the combination of both techniques, called photodynamic inactivation (PDI), is based on the fact that some natural substances act as photosensitizers, i.e., produce bioactive effects under irradiation. Notably, curcumin is a potent natural antibacterial and effective photosensitizer that is able to induce photodynamic activation in the visible light range (specifically for blue light). Some practical applications have been investigated with particular reference to food preservation from bacterial contaminants.

Comparative Evaluation of Different Chitosan Species and Derivatives as Candidate Biomaterials for Oxygen-Loaded Nanodroplet Formulations to Treat Chronic Wounds.

Persistent hypoxia is a main clinical feature of chronic wounds. Intriguingly, oxygen-loaded nanodroplets (OLNDs), filled with oxygen-solving 2H,3H-decafluoropentane and shelled with polysaccharides, have been proposed as a promising tool to counteract hypoxia by releasing a clinically relevant oxygen amount in a time-sustained manner. Here, four different types of chitosan (low or medium weight (LW or MW), glycol-(G-), and methylglycol-(MG-) chitosan) were compared as candidate biopolymers for shell manufacturing. The aim of the work was to design OLND formulations with optimized physico-chemical characteristics, efficacy in oxygen release, and biocompatibility. All OLND formulations displayed spherical morphology, cationic surfaces, ≤500 nm diameters (with LW chitosan-shelled OLNDs being the smallest), high stability, good oxygen encapsulation efficiency, and prolonged oxygen release kinetics. Upon cellular internalization, LW, MW, and G-chitosan-shelled nanodroplets did not significantly affect the viability, health, or metabolic activity of human keratinocytes (HaCaT cell line). On the contrary, MG-chitosan-shelled nanodroplets showed very poor biocompatibility. Combining the physico-chemical and the biological results obtained, LW chitosan emerges as the best candidate biopolymer for future OLND application as a skin device to treat chronic wounds.

Cyclic Nigerosyl-Nigerose as Oxygen Nanocarrier to Protect Cellular Models from Hypoxia/Reoxygenation Injury: Implications from an In Vitro Model.

Heart failure (HF) prevalence is increasing among the aging population, and the mortality rate remains unacceptably high despite improvements in therapy. Myocardial ischemia (MI) and, consequently, ischemia/reperfusion injury (IRI), are frequently the basis of HF development. Therefore, cardioprotective strategies to limit IRI are mandatory. Nanocarriers have been proposed as alternative therapy for cardiovascular disease. Controlled reoxygenation may be a promising strategy. Novel nanocarriers, such as cyclic nigerosyl-nigerose (CNN), can be innovative tools for oxygen delivery in a controlled manner. In this study we analyzed new CNN-based formulations as oxygen nanocarriers (O2-CNN), and compared them with nitrogen CNN (N2-CNN). These different CNN-based formulations were tested using two cellular models, namely, cardiomyoblasts (H9c2), and endothelial (HMEC) cell lines, at different concentrations. The effects on the growth curve during normoxia (21% O2, 5% CO2 and 74% N2) and their protective effects during hypoxia (1% O2, 5% CO2 and 94% N2) and reoxygenation (21% O2, 5% CO2 and 74% N2) were studied. Neither O2-CNN nor N2-CNN has any effect on the growth curve during normoxia. However, O2-CNN applied before hypoxia induces a 15-30% reduction in cell mortality after hypoxia/re-oxygenation when compared to N2-CNN. O2-CNN showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for the future medical application of soluble nanocarrier systems for MI treatment.

Step-by-Step Design of New Theranostic Nanoformulations: Multifunctional Nanovectors for Radio-Chemo-Hyperthermic Therapy under Physical Targeting.

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.

Tetra-(p-tolyl)antimony(III)-Containing Heteropolytungstates, [{(p-tolyl)SbIII}4(A-α-XW9O34)2]n- (X = P, As, or Ge): Synthesis, Structure, and Study of Antibacterial and Antitumor Activity.

We have synthesized and structurally characterized three tetra-(p-tolyl)antimony(III)-containing heteropolytungstates, [{(p-tolyl)SbIII}4(A-α-XW9O34)2]n- [X = PV (1-P), AsV (1-As), or GeIV (1-Ge)], in aqueous solution using conventional, one-pot procedures. The polyanions 1-P, 1-As, and 1-Ge were fully characterized in the solid state and in solution and were shown to be soluble and stable in aqueous medium at pH 7. Biological studies demonstrated that all three polyanions possess significant antibacterial and antitumor activities. The minimum inhibitory concentrations of 1-P, 1-As, and 1-Ge were determined against four kinds of bacteria, including the two pathogenic bacteria strains, Vibrio parahaemolyticus and Vibrio vulnificus. The three novel polyanions also showed high cytotoxic potency in the human cell lines A549 (non-small cell lung cancer), CH1/PA-1 (ovarian teratocarcinoma), and SW480 (colon carcinoma).

Melaleuca alternifolia Essential Oil: Evaluation of Skin Permeation and Distribution from Topical Formulations with a Solvent-Free Analytical Method.

Melaleuca alternifolia essential oil (tea tree oil) is widely used as an ingredient in skin care products because of its recognized biological activities. The European Scientific Committee on Consumer Products constantly promotes research and collection of data on both skin distribution and systemic exposure to tea tree oil components after the application of topical formulations. This study quantitatively evaluates permeation, skin layer distribution (stratum corneum, epidermis, and dermis), and release into the surrounding environment of bioactive tea tree oil markers (i.e., α-pinene, ß-pinene, α-terpinene, 1,8-cineole, γ-terpinene, 4-terpineol, α-terpineol) when a 5% tea tree oil formulation is applied at a finite dosing regimen. Permeation kinetics were studied in vitro on pig ear skin using conventional static glass Franz diffusion cells and cells ad hoc modified to monitor the release of markers into the atmosphere. Formulation, receiving phases, and skin layers were analyzed using a fully automatic and solvent-free method based on headspace solid-phase microextraction/gas chromatography-mass spectrometry. This approach affords, for the first time, to quantify tea tree oil markers in the different skin layers while avoiding using solvents and overcoming the existing methods based on solvent extraction. The skin layers contained less than 1% of each tea tree oil marker in total. Only oxygenated terpenes significantly permeated across the skin, while hydrocarbons were only absorbed at trace level. Substantial amounts of markers were released into the atmosphere.

Beyond Oncological Hyperthermia: Physically Drivable Magnetic Nanobubbles as Novel Multipurpose Theranostic Carriers in the Central Nervous System.

Magnetic Oxygen-Loaded Nanobubbles (MOLNBs), manufactured by adding Superparamagnetic Iron Oxide Nanoparticles (SPIONs) on the surface of polymeric nanobubbles, are investigated as theranostic carriers for delivering oxygen and chemotherapy to brain tumors. Physicochemical and cyto-toxicological properties and in vitro internalization by human brain microvascular endothelial cells as well as the motion of MOLNBs in a static magnetic field were investigated. MOLNBs are safe oxygen-loaded vectors able to overcome the brain membranes and drivable through the Central Nervous System (CNS) to deliver their cargoes to specific sites of interest. In addition, MOLNBs are monitorable either via Magnetic Resonance Imaging (MRI) or Ultrasound (US) sonography. MOLNBs can find application in targeting brain tumors since they can enhance conventional radiotherapy and deliver chemotherapy being driven by ad hoc tailored magnetic fields under MRI and/or US monitoring.

Biological Effect Evaluation of Glutathione-Responsive Cyclodextrin-Based Nanosponges: 2D and 3D Studies.

This study aims to evaluate the bioeffects of glutathione-responsive ß-cyclodextrin-based nanosponges (GSH-NSs) on two- (2D) and three-dimensional (3D) cell cultures. The bioeffects of two types of GSH-NS formulations, with low (GSH-NS B) and high (GSH-NS D) disulfide-bond content, were evaluated on 2D colorectal (HCT116 and HT-29) and prostatic (DU-145 and PC3) cancer cell cultures. In particular, the cellular uptake of GSH-NS was evaluated, as their effects on cell growth, mitochondrial activity, membrane integrity, cell cycle distribution, mRNA expression, and reactive oxygen species production. The effect of GSH-NSs on cell growth was also evaluated on multicellular spheroids (MCS) and a comparison of the GSH-NS cell growth inhibitory activity, in terms of inhibition concentration (IC)50 values, was performed between 2D and 3D cell cultures. A significant decrease in 2D cell growth was observed at high GSH-NS concentrations, with the formulation with a low disulfide-bond content, GSH-NS B, being more cytotoxic than the formulation with a high disulfide-bond content, GSH-NS D. The cell growth decrease induced by GSH-NS was owing to G1 cell cycle arrest. Moreover, a significant down-regulation of mRNA expression of the cyclin genes CDK1, CDK2, and CDK4 and up-regulation of mRNA expression of the cyclin inhibitor genes CDKN1A and CDKN2A were observed. On the other hand, a significant decrease in MCS growth was also observed at high GSH-NS concentrations, but not influenced by the nanosponge disulfide-bond content, with the MCS IC50 values being significantly higher than those obtained on 2D cell cultures. GSH-NSs are suitable nanocarries as they provoke limited cellular effects, as cell cycle arrest only occurred at concentrations significantly higher than those used for drug delivery.