Luminescent Alendronic Acid-Conjugated Micellar Nanostructures for Potential Application in the Bone-Targeted Delivery of Cholecalciferol.

Vitamin D, an essential micronutrient crucial for skeletal integrity and various non-skeletal physiological functions, exhibits limited bioavailability and stability in vivo. This study is focused on the development of polyethylene glycol (PEG)-grafted phospholipid micellar nanostructures co-encapsulating vitamin D3 and conjugated with alendronic acid, aimed at active bone targeting. Furthermore, these nanostructures are rendered optically traceable in the UV-visible region of the electromagnetic spectrum via the simultaneous encapsulation of vitamin D3 with carbon dots, a newly emerging class of fluorescents, biocompatible nanoparticles characterized by their resistance to photobleaching and environmental friendliness, which hold promise for future in vitro bioimaging studies. A systematic investigation is conducted to optimize experimental parameters for the preparation of micellar nanostructures with an average hydrodynamic diameter below 200 nm, ensuring colloidal stability in physiological media while preserving the optical luminescent properties of the encapsulated carbon dots. Comprehensive chemical-physical characterization of these micellar nanostructures is performed employing optical and morphological techniques. Furthermore, their binding affinity for the principal inorganic constituent of bone tissue is assessed through a binding assay with hydroxyapatite nanoparticles, indicating significant potential for active bone-targeting. These formulated nanostructures hold promise for novel therapeutic interventions to address skeletal-related complications in cancer affected patients in the future.

Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases.

Extracellular vesicles (EVs), acting as inherent nanocarriers adept at transporting a range of different biological molecules such as proteins, lipids, and genetic material, exhibit diverse functions within the gastroenteric tract. In states of normal health, they participate in the upkeep of systemic and organ homeostasis. Conversely, in pathological conditions, they significantly contribute to the pathogenesis of gastrointestinal diseases (GIDs). Isolating EVs from patients' biofluids facilitates the discovery of new biomarkers that have the potential to offer a rapid, cost-effective, and non-invasive method for diagnosing and prognosing specific GIDs. Furthermore, EVs demonstrate considerable therapeutic potential as naturally targeted physiological carriers for the intercellular delivery of therapeutic cargo molecules or as nanoscale tools engineered specifically to regulate physio-pathological conditions or disease progression. Their attributes including safety, high permeability, stability, biocompatibility, low immunogenicity, and homing/tropism capabilities contribute to their promising clinical therapeutic applications. This review will delve into various examples of EVs serving as biomarkers or nanocarriers for therapeutic cargo in the context of GIDs, highlighting their clinical potential for both functional and structural gastrointestinal conditions. The versatile and advantageous properties of EVs position them as promising candidates for innovative therapeutic strategies in advancing personalized medicine approaches tailored to the gastroenteric tract, addressing both functional and structural GIDs.

Semaglutide Modulates Extracellular Matrix Production of LX-2 Cells via Exosomes and Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to some metabolic disorders, such as central obesity and type 2 diabetes (T2D). Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide, may have therapeutic roles in MASLD associated with T2D. This study aims to investigate the molecular mechanisms underlying the effectiveness of semaglutide on MASLD in terms of progression from liver steatosis to fibrosis. We characterized exosomes from ten patients with type 2 diabetes (T2D) before (T0) and after 12 months (T12) of treatment with once-weekly subcutaneous semaglutide. Six of ten patients were considered responders to therapy (R) based on MASLD severity downgrading by at least one class according to a validated ultrasonographic (US) score. Normal hepatocytes (HEPA-RG) and stellate (LX-2) cells were challenged with exosomes from R and NR patients, isolated before and after 12 months of therapy. Exosomes from both R and NR patients isolated at T0 significantly affected LX-2 viability. After 12 months of treatment, only those isolated from R patients restored cell viability, whereas those from NR patients did not. No effects were observed on HEPA-RG cells. Exosomes at T12 from R but not from NR patients significantly decreased the production of α-SMA, a marker of LX-2 activation, a liver stellate cell model, and ph-SMAD2 and CTGF, involved in fibrosis processes. TGF-ß1 was not modulated by the exosomes of R and NR patients. As a downstream effect, Vimentin, Collagen 1A1, and Fibronectin extracellular matrix components were also downregulated, as measured by droplets digital PCR. In conclusion, these results shed light on the potential effectiveness of semaglutide in improving liver fibrosis in MASLD.

Effect of a Composite Alginate/Grape Pomace Extract Packaging Material for Improving Meat Storage.

The development of food packaging materials that reduce the production of plastic, preserving at the same time the quality of food, is a topic of great interest today for the scientific community. Therefore, this article aims to report the effectiveness of an eco-friendly packaging material based on alginic acid and grape pomace extract from Vitis vinifera L. (winemaking by-products) for storing red meat in a domestic refrigerator. Specifically, biogenic amines are considered "sentinels" of the putrefactive processes, and their presence was thus monitored. For this purpose, an experimental analytical protocol based on the use of solid-phase microextraction coupled with gas chromatography-mass spectrometry was developed during this work for the determination of six biogenic amines (butylamine, cadaverine, isobutylamine, isopentylamine, putrescine, and tyramine). Moreover, by combining the analytical results with those of pH and weight loss measurements, differential scanning calorimetry, and microbiological analysis, it was proved that the studied materials could be proposed as an alternative packaging material for storing foods of animal origin, thus lowering the environmental impact according to sustainability principles.

Pencil Graphite Electrocatalytic Sensors Modified by Pyrene Coated Reduced Graphene Oxide Decorated with Molybdenum Disulfide Nanoroses for Hydrazine and 4-Nitrophenol Detection in Real Water Samples.

Novel nanostructured platforms based on Pencil Graphite Electrodes (PGEs), modified with pyrene carboxylic acid (PCA) functionalized Reduced Graphene Oxide (rGO), and then decorated by chronoamperometry electrodeposition of MoS2 nanoroses (NRs) (MoS2NRs/PCA-rGO/PGEs) were manufactured for the electrocatalytic detection of hydrazine (N2H4) and 4-nitrophenol, pollutants highly hazardous for environment and human health. The surface morphology and chemistry of the MoS2NRs/PCA-rGO/PGEs were characterized by scanning electron microscopy (SEM), Raman, and X-ray photoelectron spectroscopy (XPS), assessing the coating of the PCA-rGO/PGEs by dense multilayers of NRs. N2H4 and 4-nitrophenol have been monitored by Differential Pulse Voltammetry (DPV), and the MoS2NRs/PCA-rGO/PGEs electroanalytical properties have been compared to the PGEs, as neat and modified by PCA-rGO. The MoS2NRs/PCA-rGO/PGEs demonstrated a higher electrochemical and electrocatalytic activity, due to their high surface area and conductivity, and very fast heterogeneous electron transfer kinetics at the interphase with the electrolyte. LODs lower than the U.S. EPA recommended concentration values in drinking water, namely 9.3 nM and 13.3 nM, were estimated for N2H4 and 4-nitrophenol, respectively and the MoS2NRs/PCA-rGO/PGEs showed good repeatability, reproducibility, storage stability, and selectivity. The effectiveness of the nanoplatforms for monitoring N2H4 and 4-nitrophenol in tap, river, and wastewater was addressed.

The oleic/palmitic acid imbalance in exosomes isolated from NAFLD patients induces necroptosis of liver cells via the elongase-6/RIP-1 pathway.

Excessive toxic lipid accumulation in hepatocytes underlies the development of non-alcoholic fatty liver disease (NAFLD), phenotypically characterized by necrosis and steato-fibrosis, whose molecular mechanism is not yet fully understood. Patients with NAFLD display an imbalanced palmitic (PA) to oleic acid (OA) ratio. Moreover, increasing experimental evidence points out a relevant involvement of the exosomal content in disease progression. Aim of the study was to highlight the PA/OA imbalance within circulating exosomes, the subsequent intracellular alterations, and the impact on NALFD. Liver cells were challenged with exosomes isolated from both healthy subjects and NAFLD patients. The exosomal PA/OA ratio was artificially modified, and biological effects were evaluated. A NAFLD-derived exosomal PA/OA imbalance impacts liver cell cycle and cell viability. OA-modified NAFLD-derived exosomes restored cellular viability and proliferation, whereas the inclusion of PA into healthy subjects-derived exosomes negatively affected cell viability. Moreover, while OA reduced the phosphorylation and activation of the necroptosis marker, Receptor-interacting protein 1 (phospho-RIP-1), PA induced the opposite outcome, alongside increased levels of stress fibers, such as vimentin and fibronectin. Administration of NAFLD-derived exosomes led to increased expression of Elongase 6 (ELOVL6), Stearoyl-CoA desaturase 1 (SCD1), Tumor necrosis factor α (TNF-α), Mixed-lineage-kinase-domain-like-protein (MLKL) and RIP-1 in the hepatocytes, comparable to mRNA levels in the hepatocytes of NAFLD patients reported in the Gene Expression Omnibus (GEO) database. Genetic and pharmacological abrogation of ELOVL6 elicited a reduced expression of downstream molecules TNF-α, phospho-RIP-1, and phospho-MLKL upon administration of NAFLD-derived exosomes. Lastly, mice fed with high-fat diet exhibited higher phospho-RIP-1 than mice fed with control diet. Targeting the Elongase 6-RIP-1 signaling pathway offers a novel therapeutic approach for the treatment of the NALFD-induced exosomal PA/OA imbalance.

Atmospheric Pressure Plasma Deposition of Hybrid Nanocomposite Coatings Containing TiO2 and Carbon-Based Nanomaterials.

Among the different applications of TiO2, its use for the photocatalytic abatement of organic pollutants has been demonstrated particularly relevant. However, the wide band gap (3.2 eV), which requires UV irradiation for activation, and the fast electron-hole recombination rate of this n-type semiconductor limit its photocatalytic performance. A strategy to overcome these limitations relies on the realization of a nanocomposite that combines TiO2 nanoparticles with carbon-based nanomaterials, such as rGO (reduced graphene oxide) and fullerene (C60). On the other hand, the design and realization of coatings formed of such TiO2-based nanocomposite coatings are essential to make them suitable for their technological applications, including those in the environmental field. In this work, aerosol-assisted atmospheric pressure plasma deposition of nanocomposite coatings containing both TiO2 nanoparticles and carbon-based nanomaterials, as rGO or C60, in a siloxane matrix is reported. The chemical composition and morphology of the deposited films were investigated for the different types of prepared nanocomposites by means of FT-IR, FEG-SEM, and TEM analyses. The photocatalytic activity of the nanocomposite coatings was evaluated through monitoring the photodegradation of methylene blue (MB) as a model organic pollutant. Results demonstrate that the nanocomposite coatings embedding rGO or C60 show enhanced photocatalytic performance with respect to the TiO2 counterpart. In particular, TiO2/C60 nanocomposites allow to achieve 85% MB degradation upon 180 min of UV irradiation.

Encapsulation of MCC950 in Liposomes Decorated with Anti-Frizzled 1 Improves Drug Bioavailability and Effectiveness in Fatty Liver Disease.

Inflammasome activation plays a crucial role in the progression to more severe stages of non-alcoholic fatty liver disease (NAFLD), representing a promising therapeutic target. MCC950 is a small molecule acting as a potent and specific inhibitor of the canonical and non-canonical activation of the NLRP3 inflammasome, but its short plasmatic half-life limits its use. Herein, we report, for the first time, the encapsulation of MCC950 in poly(ethylene glycol) (PEG) liposomes (LPs) that are specifically functionalized with an antibody against Frizzled 1 (FZD1), a g-coupled protein involved in the WNT pathway and overexpressed on inflammasome-activated macrophages. MCC950, encapsulated into PEG-LP formulations conjugated with an anti-FZD1 antibody, inhibits the NLRP3 inflammasome activation at concentrations 10 times lower than that of the free drug in THP-1 cells. Luminescent carbon dots (CDs) were also co-encapsulated with MCC950 in LPs to obtain optically traceable nanoformulations that have proved the enhanced ability of the targeted LPs to be internalized into THP-1 cells with respect to their nontargeted counterparts. Our results suggest that MCC950 encapsulation into targeted LPs represents a valuable strategy to achieve reformulation of the NLRP3 inhibitor, able to significantly curtail the threshold of MCC950 doses for inhibiting inflammasome activation, thus offering a new therapeutic approach.

One-Pot Synthesis of Dual Color-Emitting CDs: Numerical and Experimental Optimization towards White LEDs.

Carbon Dots (CDs) are fluorescent carbon-based nanoparticles that have attracted increasing attention in recent years as environment-friendly and cost-effective fluorophores. An application that can benefit from CDs in a relatively short-term perspective is the fabrication of color-converting materials in phosphor-converted white LEDs (WLEDs). In this work we present a one-pot solvothermal synthesis of polymer-passivated CDs that show a dual emission band (in the green and in the red regions) upon blue light excitation. A purposely designed numerical approach enables evaluating how the spectroscopic properties of such CDs can be profitable for application in WLEDs emulating daylight characteristics. Subsequently, we fabricate nanocomposite coatings based on the dual color-emitting CDs via solution-based strategies, and we compare their color-converting properties with those of the simulated ones to finally accomplish white light emission. The combined numerical and experimental approach can find a general use to reduce the number of experimental trial-and-error steps required for optimization of CD optical properties for lighting application.

Life Cycle Assessment of UV-C based treatment systems for the removal of compounds of emerging concern from urban wastewater.

In the last decades particular attention is being paid to the efficient and effective removal of compounds of emerging concern (CECs) present in wastewater before their eventual reuse or disposal. Several technologies have been developed for the degradation of CECs in aqueous matrix, in this regard advanced oxidation processes (AOPs) represent a nascent technological solution developed on a laboratory scale with applications on a prototype scale. The experimental evidences have shown that AOPs processes can oxidize numerous organic compounds in a much faster and more efficient way than that of the most common disinfection processes. The most common AOPs processes are those that involve the use of H2O2/UV, O3/UV, H2O2/O3, H2O2/O3/UV, Fenton and photo-Fenton. The aim of this work is to illustrate the results of a comparative LCA study of a laboratory scale UV-C photoreactor for the tertiary treatment of urban wastewater of three treatment systems (UV-C, UV-C + H2O2 e UV-C + TiO2). In particular, the specific objective is to evaluate, from an environmental point of view, an innovative advanced oxidation system based on nanostructures TiO2 immobilized on a stainless steel mesh. Compared to the UV-C photolysis reference system, the addition of hydrogen peroxide reduces the total environmental impact of the system by almost 75 %, while the use of the stainless-steel mesh coated by the nanostructures titanium dioxide reduces the UV-C environmental impact by 30 %. These results are due to the lower energy consumption of these last treatments compared to photolysis alone. The main impacts of the three systems are related to the electric power consumption of the centrifugal pump (63-64 %) and of the UV-C lamp (32-33 %). The LCA applied to these systems has shown that TiO2 assisted photocatalysis is not yet advantageous from an environmental point of view and that, therefore, the efficiency of the system needs to be improved.

Au nanoparticles decorated nanographene oxide-based platform: Synthesis, functionalization and assessment of photothermal activity.

A novel hybrid nanocomposite formed of carboxylated Nano Graphene Oxide (c-NGO), highly densely decorated by monodisperse citrate-coated Au nanoparticles (c-NGO/Au NPs), is synthesized and thoroughly characterized for photothermal applications. A systematic investigation of the role played by the synthetic parameters on the Au NPs decoration of the c-NGO platform is performed, comprehensively studying spectroscopic and morphological characteristics of the achieved nanostructures, thus elucidating their still not univocally explained synthesis mechanism. Remarkably, the Au NPs coating density of the c-NGO sheets is much higher than state-of-the-art systems with analogous composition prepared with different approaches, along with a higher NPs size dispersion. A novel theoretical approach for estimating the average number of NPs per sheet, combining DLS and TEM results, is developed. The assessment of the c-NGO/Au NPs photothermal activity is performed under continuous wave (CW) laser irradiation, at 532 nm and 800 nm, before and after functionalization with PEG-SH. c-NGO/Au NPs composite behaves as efficient photothermal agent, with a light into heat conversion ability higher than that of the single components. The c-NGO/Au NPs compatibility for photothermal therapy is assessed by in vitro cell viability tests, which show no significant effects of c-NGO/Au NPs, as neat and PEGylated, on cell metabolic activity under the investigated conditions. These results demonstrate the great potential held by the prepared hybrid nanocomposite for photothermal conversion technologies, indicating it as particularly promising platform for photothermal ablation of cancer cells.

Understanding the Effect of the Synthetic Method and Surface Chemistry on the Properties of CsPbBr3 Nanoparticles.

Over the last decade, the attractive properties of CsPbBr3 nanoparticles (NPs) have driven ever-increasing progress in the development of synthetic procedures to obtain high-quality NPs at high concentrations. Understanding how the properties of NPs are influenced by the composition of the reaction mixture in combination with the specific synthetic methodology is crucial, both for further elucidating the fundamental characteristics of this class of materials and for their manufacturing towards technological applications. This work aims to shed light on this aspect by synthesizing CsPbBr3 NPs by means of two well-assessed synthetic procedures, namely, hot injection (HI) and ligand-assisted reprecipitation (LARP) in non-polar solvents, using PbBr2 and Cs2CO3 as precursors in the presence of already widely investigated ligands. The overall goal is to study and compare the properties of the NPs to understand how each synthetic method influences the NPs' size and/or the optical properties. Reaction composition and conditions are purposely tuned towards the production of nanocubes with narrow size distribution, high emission properties, and the highest achievable concentration. As a result, the formation of bulk crystals as precipitate in LARP limits the achievement of a highly concentrated NP solution. The size of the NPs obtained by LARP seems to be poorly affected by the ligands' nature and the excess bromide, as consequence of bromide-rich solvation agents, effectively results in NPs with excellent emission properties. In contrast, NPs synthesized by HI exhibit high reaction yield, diffusion growth-controlled size, and less striking emission properties, probably ascribed to a bromide-deficient condition.

Electrochemical Sensors Based on Au Nanoparticles Decorated Pyrene-Reduced Graphene Oxide for Hydrazine, 4-Nitrophenol and Hg2+ Detection in Water.

Monitoring hazardous chemical compounds such as hydrazine (N2H4), 4-nitrophenol (4-NP) and Hg2+ in natural water resources is a crucial issue due to their toxic effects on human health and catastrophic impact on the environment. Electrochemical nanostructured platforms integrating hybrid nanocomposites based on graphene derivatives and inorganic nanoparticles (NPs) are of great interest for such a purpose. In this work, disposable screen-printed carbon electrodes (SPCEs) have been modified with a hybrid nanocomposite formed by reduced graphene oxide (RGO), functionalized by 1-pyrene carboxylic acid (PCA), and decorated by colloidal Au NPs. These hybrid platforms have been tested for the electrocatalytic detection of N2H4 and 4-NP by differential pulse voltammetry and have been modified with an electropolymerized film of Hg2+ ions imprinted polycurcumin for the electroanalytical detection of Hg2+ by DPV. LODs, lower and in line with the lowest ones reported for state-of-the-art electrochemical sensors, integrating similar Au-graphene < nanocomposites, have been estimated. Additionally, good repeatability, reproducibility, and storage stability have been assessed, as well as a high selectivity in the presence of a 100-fold higher concentration of interfering species. The applicability of the proposed platforms for the detection of the compounds in real complex matrices, such as tap and river water samples, has been effectively demonstrated.

Photocatalytic Investigation of Aerosol-Assisted Atmospheric Pressure Plasma Deposited Hybrid TiO2 Containing Nanocomposite Coatings.

We report on the aerosol-assisted atmospheric-pressure plasma deposition onto a stainless-steel woven mesh of a thin nanocomposite coating based on TiO2 nanoparticles hosted in a hybrid organic−inorganic matrix, starting from nanoparticles dispersed in a mixture of hexamethyldisiloxane and isopropyl alcohol. The stainless-steel mesh was selected as an effective support for the possible future technological application of the coating for photocatalytically assisted water depollution. The prepared coatings were thoroughly investigated from the chemical and morphological points of view and were demonstrated to be photocatalytically active in the degradation of an organic molecule, used as a pollutant model, in water upon UV light irradiation. In order to optimize the photocatalytic performance, different approaches were investigated for the coating's realization, namely (i) the control of the deposition time and (ii) the application of a postdeposition O2 plasma treatment on the pristine coatings. Both strategies were found to be able to increase the photocatalytic activity, and, remarkably, their combination resulted in a further enhancement of the photoactivity. Indeed, the proposed combined approach allowed a three-fold increase in the kinetic constant of the degradation reaction of the model dye methylene blue with respect to the pristine coating. Interestingly, the chemical and morphological characterizations of all the prepared coatings were able to account for the enhancement of the photocatalytic performance. Indeed, the presence of the TiO2 nanoparticles on the outmost surface of the film confirmed the accessibility of the photocatalytic sites in the nanocomposite and reasonably explained the enhanced photocatalytic performance. In addition, the sustained photoactivity (>5 cycles of use) of the nanocomposites was demonstrated.

NIR-Absorbing Mesoporous Silica-Coated Copper Sulphide Nanostructures for Light-to-Thermal Energy Conversion.

Plasmonic nanostructures, featuring near infrared (NIR)-absorption, are rising as efficient nanosystems for in vitro photothermal (PT) studies and in vivo PT treatment of cancer diseases. Among the different materials, new plasmonic nanostructures based on Cu2-xS nanocrystals (NCs) are emerging as valuable alternatives to Au nanorods, nanostars and nanoshells, largely exploited as NIR absorbing nanoheaters. Even though Cu2-xS plasmonic properties are not linked to geometry, the role played by their size, shape and surface chemistry is expected to be fundamental for an efficient PT process. Here, Cu2-xS NCs coated with a hydrophilic mesoporous silica shell (MSS) are synthesized by solution-phase strategies, tuning the core geometry, MSS thickness and texture. Besides their loading capability, the silica shell has been widely reported to provide a more robust plasmonic core protection than organic molecular/polymeric coatings, and improved heat flow from the NC to the environment due to a reduced interfacial thermal resistance and direct electron-phonon coupling through the interface. Systematic structural and morphological analysis of the core-shell nanoparticles and an in-depth thermoplasmonic characterization by using a pump beam 808 nm laser, are carried out. The results suggest that large triangular nanoplates (NPLs) coated by a few tens of nanometers thick MSS, show good photostability under laser light irradiation and provide a temperature increase above 38 °C and a 20% PT efficiency upon short irradiation time (60 s) at 6 W/cm2 power density.

Polydopamine-Coated Magnetic Iron Oxide Nanoparticles: From Design to Applications.

Magnetic iron oxide nanoparticles have been extensively investigated due to their applications in various fields such as biomedicine, sensing, and environmental remediation. However, they need to be coated with a suitable material in order to make them biocompatible and to add new functionalities on their surface. This review is intended to give a comprehensive overview of recent advantages and applications of iron oxide nanoparticles coated by polydopamine film. The synthesis method of magnetic nanoparticles, their functionalization with bioinspired materials and (in particular) with polydopamine are discussed. Finally, some interesting applications of polydopamine-coated magnetic iron oxide nanoparticles will be pointed out.

Exosomal FZD-7 Expression Is Modulated by Different Lifestyle Interventions in Patients with NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.

Magnetic implants in vivo guiding sorafenib liver delivery by superparamagnetic solid lipid nanoparticles.

HYPOTHESIS: Solid lipid nanoparticles (SLNs), co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib, have been exploited for magnetic-guided drug delivery to the liver. Two different magnetic configurations, both comprising two small magnets, were under-skin implanted to investigate the effect of the magnetic field topology on the magnetic SLNP accumulation in liver tissues. A preliminary simulation analysis was performed to predict the magnetic field topography for each tested configuration. EXPERIMENTS: SLNs were prepared using a hot homogenization approach and characterized using complementary techniques. Their in vitro biological behavior was assessed in HepG-2 liver cancer cells; wild-type mice were used for the in vivo study. The magnet configuration that resulted in a higher magnetic targeting efficiency was investigated by evaluating the iron content in homogenated murine liver tissues. FINDINGS: SLNs, characterized by an average size smaller than 200 nm, retained their superparamagnetic behavior and relevant molecular resonance imaging properties as negative contrast agents. The evaluation of iron accumulation in the liver tissues was consistent with the magnetic induction profile of each magnet configuration, concurring with the results predicted by simulation analysis and obtained by measurements in living mice.

Luminescent PLGA Nanoparticles for Delivery of Darunavir to the Brain and Inhibition of Matrix Metalloproteinase-9, a Relevant Therapeutic Target of HIV-Associated Neurological Disorders.

Human immunodeficiency virus (HIV) can independently replicate in the central nervous system (CNS) causing neurocognitive impairment even in subjects with suppressed plasma viral load. The antiretroviral drug darunavir (DRV) has been approved for therapy of HIV-infected patients, but its efficacy in the treatment of HIV-associated neurological disorders (HAND) is limited due to the low penetration through the blood-brain barrier (BBB). Therefore, innovations in DRV formulations, based on its encapsulation in optically traceable nanoparticles (NPs), may improve its transport through the BBB, providing, at the same time, optical monitoring of drug delivery within the CNS. The aim of this study was to synthesize biodegradable polymeric NPs loaded with DRV and luminescent, nontoxic carbon dots (C-Dots) and investigate their ability to permeate through an artificial BBB and to inhibit in vitro matrix metalloproteinase-9 (MMP-9) that represents a factor responsible for the development of HIV-related neurological disorders. Biodegradable poly(lactic-co-glycolic) acid (PLGA)-based nanoformulations resulted characterized by an average hydrodynamic size less than 150 nm, relevant colloidal stability in aqueous medium, satisfactory drug encapsulation efficiency, and retained emitting optical properties in the visible region of the electromagnetic spectrum. The assay on the BBB artificial model showed that a larger amount of DRV was able to cross BBB when incorporated in the PLGA NPs and to exert an enhanced inhibition of matrix metalloproteinase-9 (MMP-9) expression levels with respect to free DRV. The overall results reveal the great potential of this class of nanovectors of DRV for an efficacious treatment of HANDs.