RGD-tagging of star-shaped PLA-PEG micellar nanoassemblies enhances doxorubicin efficacy against osteosarcoma.

We developed cyclic RGD-tagged polymeric micellar nanoassemblies for sustained delivery of Doxorubicin (Dox) endowed with significant cytotoxic effect against MG63, SAOS-2, and U2-OS osteosarcoma cells without compromising the viability of healthy osteoblasts (hFOBs). Targeted polymeric micellar nanoassemblies (RGD-NanoStar@Dox) enabled Dox to reach the nucleus of MG63, SAOS-2, and U2-OS cells causing the same cytotoxic effect as free Dox, unlike untargeted micellar nanoassemblies (NanoStar@Dox) which failed to reach the nucleus and resulted ineffective, demonstrating the crucial role of cyclic RGD peptide in driving cellular uptake and accumulation mechanisms in osteosarcoma cells. Micellar nanoassemblies were obtained by nanoformulation of three-armed star PLA-PEG copolymers properly synthetized with and without decoration with the cyclic-RGDyK peptide (Arg-Gly-Asp-D-Tyr-Lys). The optimal RGD-NanoStar@Dox nanoformulation obtained by nanoprecipitation method (8 % drug loading; 35 % encapsulation efficiency) provided a prolonged and sustained drug release with a rate significantly lower than the free drug under the same experimental conditions. Moreover, the nanosystem preserved Dox from the natural degradation occurring under physiological conditions (i.e., dimerization and consequent precipitation) serving as a slow-release "drug reservoir" ensuring an extended biological activity over the time.

Special Issue "Materials for Photobiology".

Photobiology is a challenging research area that aims to explore the interactions between light and living organisms and their biological consequences, with applications in the fields of photomedicine, photo(nano)technology, photosynthesis, and photosensory biology [...].

Screen-Printed Carbon Electrodes with Cationic Cyclodextrin Carbon Nanotubes and Ferrocenyl-Carnosine for Electrochemical Sensing of Hg(II).

The study reports the use of nanoassembly based on cationic cyclodextrin carbon nanotubes (CNT-CDs) and ferrocenylcarnosine (FcCAR) for electrochemical sensing of Hg(II) in aqueous solution. ß-cyclodextrins (CDs) were grafted onto CNTs by a click chemistry reaction between heptakis-(6-azido-6-deoxy)-ß-cyclodextrin and alkyne-terminated CNTs. The cationic amine groups on the CD units were produced by the subsequent reduction of the residual nitrogen groups. The chemical composition and morphology of CNT-CDs were analyzed by X-ray photoelectron spectroscopy, scanning electron microscopy, and thermogravimetric analysis. A N,N-dimethylformamide dispersion of CNT-CDs was cast on the surface of screen-printed carbon electrodes (SPCEs), and the electrochemical response was evaluated by cyclic voltammetry (CV) using [Fe(CN)6]3- as the redox probe. The ability of SPCE/CNT-CD to significantly enhance the electroactive properties of the redox probe was combined with a suitable recognition element (FcCAR) for Hg(II). The electrochemical response of the CNT-CD/FcCAR nanoassembly was evaluated by CV and electrochemical impedance spectroscopy. The analytical performance of the Hg(II) sensor was evaluated by differential pulsed voltammetry and chronoamperometry. The oxidative peak current showed a linear concentration dependence in the range of 1-100 nM, with a sensitivity of 0.12 µA/nM, a limit of detection of 0.50 nM, and a limit of quantification of 1 nM.

Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives.

The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered a highly conserved viral target. Disruption of the catalytic activity of Mpro produces a detrimental effect on the course of the infection, making this target one of the most attractive for the treatment of COVID-19. The current success of the SARS-CoV-2 Mpro inhibitor Nirmatrelvir, the first oral drug for the treatment of severe forms of COVID-19, has further focused the attention of researchers on this important viral target, making the search for new Mpro inhibitors a thriving and exciting field for the development of antiviral drugs active against SARS-CoV-2 and related coronaviruses.

Harnessing the power of PLA-PEG nanoparticles for Linezolid delivery against methicillin-resistant Staphylococcus aureus.

This study deals with the development of novel poly(lactic acid)-poly(ethylene glycol) nanoparticles (PLA-PEG NPs) for the efficient and prolonged delivery of Linezolid (LNZ), a synthetic antibacterial agent used against methicillin-resistant Staphylococcus aureus (MRSA). A two-step synthetic strategy based on carbodiimide coupling and copper-catalyzed azide-alkyne cycloaddition was first exploited for the conjugation of PLA with PEG. The encapsulation of LNZ into medium-molecular-weight PLA-PEG NPs was carried out by different methods including nanoprecipitation and dialysis. The optimal PLA-PEG@LNZ nanoformulation resulted in 3.5% LNZ payload (15% encapsulation efficiency, with a 10:3 polymer to drug mass ratio) and sustained release kinetics with 65% of entrapped antibiotic released within 80 h. Moreover, the zeta potential values (from -31 to -39 mV) indicated a good stability without agglomeration even after freeze-drying and lyophilization. The PLA-PEG@LNZ NPs exerted antimicrobial activity against a panel of Gram-positive bacteria responsible for human infections, such as Staphylococcus aureus including MRSA, Staphylococcus epidermidis, Staphylococcus lugdunensis and vancomycin-resistant Enterococcus faecium (VREfm). Moreover, PLA-PEG@LNZ NPs showed inhibitory activity on both planktonic growth and preformed biofilm of MRSA. The antibacterial activity of LNZ incorporated in polymeric NPs was well preserved and the nanosystem served as an antibiotic enhancer with a potential role in MRSA-associated infections management.

Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study.

Idebenone (IDE), a synthetic short-chain analogue of coenzyme Q10, is a potent antioxidant able to prevent lipid peroxidation and stimulate nerve growth factor. Due to these properties, IDE could potentially be active towards cerebral disorders, but its poor water solubility limits its clinical application. Octanoyl-ß-cyclodextrin is an amphiphilic cyclodextrin (ACyD8) bearing, on average, ten octanoyl substituents able to self-assemble in aqueous solutions, forming various typologies of supramolecular nanoassemblies. Here, we developed nanoparticles based on ACyD8 (ACyD8-NPs) for the potential intranasal administration of IDE to treat neurological disorders, such as Alzheimer's Disease. Nanoparticles were prepared using the nanoprecipitation method and were characterized for their size, zeta potential and morphology. STEM images showed spherical particles, with smooth surfaces and sizes of about 100 nm, suitable for the proposed therapeutical aim. The ACyD8-NPs effectively loaded IDE, showing a high encapsulation efficiency and drug loading percentage. To evaluate the host/guest interaction, UV-vis titration, mono- and two-dimensional NMR analyses, and molecular modeling studies were performed. IDE showed a high affinity for the ACyD8 cavity, forming a 1:1 inclusion complex with a high association constant. A biphasic and sustained release of IDE was observed from the ACyD8-NPs, and, after a burst effect of about 40%, the release was prolonged over 10 days. In vitro studies confirmed the lack of toxicity of the IDE/ACyD8-NPs on neuronal SH-SY5Y cells, and they demonstrated their antioxidant effect upon H2O2 exposure, as a general source of ROS.

Thermodynamic and voltammetric study on carnosine and ferrocenyl-carnosine.

A potentiometric study on the interactions of L-carnosine (CAR) (2-[(3-aminopropanoyl)amino]-3-(1H-imidazol-5-yl)propanoic acid) with two toxic metal cations, Hg2+ and Cd2+, is reported here. The elucidation of the metal (M2+)-CAR interactions in aqueous solution highlighted the speciation model for each system, the dependence of the formation constants of the complex species on ionic strength (0.15 ≤ I/mol L-1 ≤ 1) and temperature (288.15 ≤ T/K ≤ 310.15) and changes in enthalpy and entropy. The sequestering ability of CAR towards the two metal ions was quantified and compared with that with Pb2+, previously determined. Considering the complexing ability of CAR and its unclear electrochemical properties, a more electroactive derivative, the ferrocenyl-carnosine (FcCAR), was synthesized and its complexing ability was evaluated by UV-vis spectroscopy. FcCAR electrochemical properties were investigated by Cyclic Voltammetry (CV) and Differential Pulse Voltammetry (DPV) on Screen-Printed Electrodes (SPEs), to evaluate its sensing properties. Electrochemical responses in the presence of Hg2+ and Pb2+ have been shown to be promising for the electrochemical detection of these metal cations in aqueous environment.

From speciation study to removal of Pb2+ from natural waters by a carnosine-based polyacrylamide/azlactone copolymer.

A deep speciation study on L-carnosine (CAR) and Pb2+ system was performed in aqueous solution with the aim to assess its potential use as a sequestering agent of metal cation. To determine the best conditions for Pb2+ complexation, potentiometric measurements were carried out over a wide range of ionic strength (0.15 ≤ I/≤ 1 mol/L) and temperature (15 ≤ T/°C ≤ 37), and thermodynamic interaction parameters (logß, ΔH, ΔG and TΔS) were determined. The speciation studies allowed us to simulate sequestration ability of CAR toward Pb2+ under different conditions of pH, ionic strength and temperature and to establish a priori the conditions for the best removal performance, i.e., pH > 7 and I = 001 mol/L. This preliminary investigation was very useful in optimizing removal procedures and limiting subsequent experimental measurements for adsorption tests. Therefore, to exploit the binding ability of CAR for Pb2+ removal from aqueous solutions, CAR was covalently grafted on an azlactone-activated beaded-polyacrylamide resin (AZ) using an efficient click coupling reaction (78.3% of coupling efficiency). The carnosine-based resin (AZCAR) was analyzed by ThermoGravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC) and Differential Thermal Analysis (DTA). Morphology, surface area and pore size distribution were studied through a combination of Scanning Electron Microscope (SEM) and adsorption/desorption of N2 analyses according to the Brunauer-Emmett-Teller (BET) and Barret-Johner-Halenda (BJH) approaches. The adsorption capacity of AZCAR toward Pb2+ was investigated under conditions simulating the ionic strength and pH of different natural waters. The time needed to reach equilibrium in the adsorption process was 24 h, and the best performance was obtained at pH > 7, typical of most natural waters, with removal efficiency ranging from 90.8% (at I = 0.7 mol/L) to 99.0 (at I = 0.001 mol/L).

Supramolecular assembly of pentamidine and polymeric cyclodextrin bimetallic core-shell nanoarchitectures.

Advanced nanoscale antimicrobials, originated from the combination of noble metal nanoparticles (NPs) with conventional antimicrobial drugs, are considered the next generation of antimicrobial agents. Therefore, there is an increasing demand for rapid, eco-friendly, and relatively inexpensive synthetic approaches for the preparation of nontoxic metallic nanostructures endowed with unique physicochemical properties. Recently, we have proposed a straightforward synthetic strategy that exploits the properties of polymeric ß-cyclodextrin (PolyCD) to act as both the reducing and stabilizing agent to produce monodispersed and stable gold-based NPs either as monometallic (nanoG) structures or core-shell bimetallic (nanoGS) architectures with an external silver layer. Here, we describe the preparation of a supramolecular assembly between nanoGS and pentamidine, an antileishmanial drug endowed with a wide range of therapeutic properties (i.e., antimicrobial, anti-inflammatory, and anticancer). The physicochemical characterization of the supramolecular assembly (nanoGSP) in terms of size and colloidal stability was investigated by complementary spectroscopic techniques, such as UV-vis, ζ-potential, and dynamic light scattering (DLS). Furthermore, the role of PolyCD during the reduction/stabilization of metal NPs was investigated for the first time by NMR spectroscopy.

Three-armed RGD-decorated starPLA-PEG nanoshuttle for docetaxel delivery.

A novel star-shaped amphiphilic copolymer based on three poly(lactide)-block-poly(ethylene glycol) (PLA-PEG) terminal arms extending from a glycerol multifunctional core was newly synthesized and decorated with the tumor-targeting ligand cyclic-RGDyK peptide (Arg-Gly-Asp-D-Tyr-Lys) to be eventually formulated in polymeric micelles incorporating a suitable anticancer drug (i.e., Docetaxel, DTX; drug loading 16 %, encapsulation efficiency 69 %). The biological profile of unloaded micelles (RGD-NanoStar) was studied on Human Adipose-derived Mesenchymal Stem Cells (Ad-MSCs) as health control, pointing out the absence of toxicity. Surprisingly, an unprecedented effect on cell viability was exerted by RGD-NanoStar, comparable to that of the free DTX, on tumoral MDA-MB 468 Human Breast Adenocarcinoma cells, specifically starting from 48 h of culture (about 40 % and 60 % of dead cells at 48 and 72 h, respectively, at all tested concentrations). RGD-NanoStar reduced the cell viability also of tumoral U87 Human Glioblastoma cells, compared to cells only, at 72 h (about 25 % of dead cells) demonstrating a time-dependent effect exerted by the highest concentrations. The effects of DTX-loaded micelles (RGD-NanoStar/DTX) on U87 and MDA-MB 468 cell lines were evaluated by MTT, cell morphology analysis, and scratch test. A compromised cell morphology was observed without significant difference between DTX-treated and RGD-NanoStar/DTX - treated cells, especially in U87 cell line. Although no apparent benefit emerged from the drug incorporation into the nanosystem by MTT assay, the scratch test revealed a statistically significant inhibition of tumoral cell migration on both cell lines, confirming the well-known role of DTX in inhibiting cell movements even when loaded on polymeric micelles. Specifically, only 43 µm distance was covered by U87 cells after 30 h culture with RGD-NanoStar/DTX (30 µg/mL) compared to 73 µm in the presence of free DTX at the same concentration; more interestingly, a total absence of MDA-MB 468 cell movements was detected at 30 h compared to about 50 µm distance covered by cells in the presence of free DTX (10 µg/mL). The stronger inhibitory activity on cell migration of RGD-NanoStar/DTX compared to the free drug in both cell lines at 30 h attested for a good ability of the drug-loaded nanocarrier to reduce tumor propagation and invasiveness, enhancing the typical effect of DTX on metastatization.

Linezolid nanoAntiobiotics and SERS-nanoTags based on polymeric cyclodextrin bimetallic core-shell nanoarchitectures.

We describe a mild, ecofriendly, and straightforward two-step strategy for making core-shell Au@Ag bimetallic nanoparticles (BMNPs) for antibacterial nanomedicine and SERS imaging. The synthesis exploits the unique properties of the cationic polymeric cyclodextrin (PolyCD) as both reducing and stabilizing agent to obtain, monodispersed and stable Au@Ag BMNPs. PolyCD-driven protocol includes the synthesis of PolyCD-coated Au monometallic nanoparticles (MNPs) as a seed material for the subsequent growing of a silver shell. PolyCD was produced by polymerization of the azido modified ßCD monomers with epichlorohydrin and subsequent reduction of azido derivative. The amino groups, as hydrochloride salts (one for CD ring), are pivotal for the formation of BMNPs in mild conditions. Nanoantibiotics and SERS-nanoTag were prepared by complexation of Au@Ag BMNPs with Linezolid (Lz) and 4-mercaptophenyl boronic acid, respectively. Au@Ag@Lz complexes showed a good antibacterial activity against all tested microorganisms including the methicillin resistant Staphylococcus aureus (MRSA).

State of the Art on Green Route Synthesis of Gold/Silver Bimetallic Nanoparticles.

Recently, bimetallic nanoparticles (BMNPs) blending the properties of two metals in one nanostructured system have generated enormous interest due to their potential applications in various fields including biosensing, imaging, nanomedicine, and catalysis. BMNPs have been developed later with respect to the monometallic nanoparticles (MNPs) and their physicochemical and biological properties have not yet been comprehensively explored. The manuscript aims at collecting the main design criteria used to synthetize BMNPs focusing on green route synthesis. The influence of experimental parameters such as temperature, time, reagent concentrations, capping agents on the particle growth and colloidal stability are examined. Finally, an overview of their nanotechnological applications and biological profile are presented.

Cancer-Related Intracellular Signalling Pathways Activated by DOXorubicin/Cyclodextrin-Graphene-Based Nanomaterials.

In the last decade, nanotechnological progress has generated new opportunities to improve the safety and efficacy of conventional anticancer therapies. Compared with other carriers, graphene nanoplatforms possess numerous tunable functionalities for the loading of multiple bioactive compounds, although their biocompatibility is still a debated concern. Recently, we have investigated the modulation of genes involved in cancer-associated canonical pathways induced by graphene engineered with cyclodextrins (GCD). Here, we investigated the GCD impact on cells safety, the HEp-2 responsiveness to Doxorubicin (DOX) and the cancer-related intracellular signalling pathways modulated by over time exposure to DOX loaded on GCD (GCD@DOX). Our studies evidenced that both DOX and GCD@DOX induced p53 and p21 signalling resulting in G0/G1 cell cycle arrest. A genotoxic behaviour of DOX was reported via detection of CDK (T14/Y15) activation and reduction of Wee-1 expression. Similarly, we found a cleavage of PARP by DOX within 72 h of exposure. Conversely, GCD@DOX induced a late cleavage of PARP, which could be indicative of less toxic effect due to controlled release of the drug from the GCD nanocarrier. Finally, the induction of the autophagy process supports the potential recycling of DOX with the consequent limitation of its toxic effects. Together, these findings demonstrate that GCD@DOX is a biocompatible drug delivery system able to evade chemoresistance and doxorubicin toxicity.

KLVFF oligopeptide-decorated amphiphilic cyclodextrin nanomagnets for selective amyloid beta recognition and fishing.

Recognition and capture of amyloid beta (Aß) is a challenging task for the early diagnosis of neurodegenerative disorders, such as Alzheimer's disease. Here, we report a novel KLVFF-modified nanomagnet based on magnetic nanoparticles (MNP) covered with a non-ionic amphiphilic ß-cyclodextrin (SC16OH) and decorated with KLVFF oligopeptide for the self-recognition of the homologous amino-acids sequence of Aß to collect Aß (1-42) peptide from aqueous samples. MNP@SC16OH and MNP@SC16OH/Ada-Pep nanoassemblies were fully characterized by complementary techniques both as solid powders and in aqueous dispersions. Single domain MNP@SC16OH/Ada-Pep nanomagnets of 20-40 nm were observed by TEM analysis. DLS and ζ-potential measurements revealed that MNP@SC16OH nanoassemblies owned in aqueous dispersion a hydrodynamic radius of about 150 nm, which was unaffected by Ada-Pep decoration, while the negative ζ-potential of MNP@SC16OH (-40 mV) became less negative (-30 mV) in MNP@SC16OH/Ada-Pep, confirming the exposition of positively charged KLVFF on nanomagnets surface. The ability of MNP@SC16OH/Ada-Pep to recruit Aß (1-42) in aqueous solution was evaluated by MALDI-TOF and compared with the ineffectiveness of undecorated MNP@SC16OH and VFLKF scrambled peptide-decorated nanoassemblies (MNP@SC16OH/Ada-scPep), pointing out the selectivity of KLVFF-decorated nanohybrid towards Aß (1-42). Finally, the property of nanomagnets to extract Aß in conditioned medium of cells over-producing Aß peptides was investigated as proof of concept of effectiveness of these nanomaterials as potential diagnostic tools.

Recent Advances and Challenges in Gene Delivery Mediated by Polyester-Based Nanoparticles.

Gene therapy is a promising approach for the treatment of several diseases, such as chronic or viral infections, inherited disorders, and cancer. The cellular internalization of exogenous nucleic acids (NA) requires efficient delivery vehicles to overcome their inherent pharmacokinetic drawbacks, e.g. electrostatic repulsions, enzymatic degradation, limited cellular uptake, fast clearance, etc. Nanotechnological advancements have enabled the use of polymer-based nanostructured biomaterials as safe and effective gene delivery systems, in addition to viral vector delivery methods. Among the plethora of polymeric nanoparticles (NPs), this review will provide a comprehensive and in-depth summary of the polyester-based nanovehicles, including poly(lactic-co-glycolic acid) (PLGA) and polylactic acid (PLA) NPs, used to deliver a variety of foreign NA, e.g. short interfering RNA (siRNA), messenger RNA (mRNA), and plasmid DNA (pDNA). The article will review the versatility of polyester-based nanocarriers including their recent application in the delivery of the clustered, regularly-interspaced, short palindromic repeats/Cas (CRISPR/Cas) genome editing system for treating gene-related diseases. The remaining challenges and future trend of the targeted delivery of this revolutionary genome-editing system will be discussed. Special attention will be given to the pivotal role of nanotechnology in tackling emerging infections such as coronavirus disease 2019 (COVID-19): ground-breaking mRNA vaccines delivered by NPs are currently used worldwide to fight the pandemic, pushing the boundaries of gene therapy.

Shedding Light on the Chemistry and the Properties of Münchnone Functionalized Graphene.

Münchnones are mesoionic oxazolium 5-oxides with azomethine ylide characteristics that provide pyrrole derivatives by a 1,3-dipolar cycloaddition (1,3-DC) reaction with acetylenic dipolarophiles. Their reactivity was widely exploited for the synthesis of small molecules, but it was not yet investigated for the functionalization of graphene-based materials. Herein, we report our results on the preparation of münchnone functionalized graphene via cycloaddition reactions, followed by the spontaneous loss of carbon dioxide and its further chemical modification to silver/nisin nanocomposites to confer biological properties. A direct functionalization of graphite flakes into few-layers graphene decorated with pyrrole rings on the layer edge was achieved. The success of functionalization was confirmed by micro-Raman and X-ray photoelectron spectroscopies, scanning transmission electron microscopy, and thermogravimetric analysis. The 1,3-DC reactions of münchnone dipole with graphene have been investigated using density functional theory to model graphene. Finally, we explored the reactivity and the processability of münchnone functionalized graphene to produce enriched nano biomaterials endowed with antimicrobial properties.

Oxazolidinone Antibiotics: Chemical, Biological and Analytical Aspects.

This review covers the main aspects concerning the chemistry, the biological activity and the analytical determination of oxazolidinones, the only new class of synthetic antibiotics advanced in clinical use over the past 50 years. They are characterized by a chemical structure including the oxazolidone ring with the S configuration of substituent at C5, the acylaminomethyl group linked to C5 and the N-aryl substituent. The synthesis of oxazolidinones has gained increasing interest due to their unique mechanism of action that assures high antibiotic efficiency and low susceptibility to resistance mechanisms. Here, the main features of oxazolidinone antibiotics licensed or under development, such as Linezolid, Sutezolid, Eperezolid, Radezolid, Contezolid, Posizolid, Tedizolid, Delpazolid and TBI-223, are discussed. As they are protein synthesis inhibitors active against a wide spectrum of multidrug-resistant Gram-positive bacteria, their biological activity is carefully analyzed, together with the drug delivery systems recently developed to overcome the poor oxazolidinone water solubility. Finally, the most employed analytical techniques for oxazolidinone determination in different matrices, such as biological fluids, tissues, drugs and natural waters, are reviewed. Most are based on HPLC (High Performance Liquid Chromatography) coupled with UV-Vis or mass spectrometer detectors, but, to a lesser extent are also based on spectrofluorimetry or voltammetry.

SARS-CoV-2 Mpro: A Potential Target for Peptidomimetics and Small-Molecule Inhibitors.

The uncontrolled spread of the COVID-19 pandemic caused by the new coronavirus SARS-CoV-2 during 2020-2021 is one of the most devastating events in the history, with remarkable impacts on the health, economic systems, and habits of the entire world population. While some effective vaccines are nowadays approved and extensively administered, the long-term efficacy and safety of this line of intervention is constantly under debate as coronaviruses rapidly mutate and several SARS-CoV-2 variants have been already identified worldwide. Then, the WHO's main recommendations to prevent severe clinical complications by COVID-19 are still essentially based on social distancing and limitation of human interactions, therefore the identification of new target-based drugs became a priority. Several strategies have been proposed to counteract such viral infection, including the repurposing of FDA already approved for the treatment of HIV, HCV, and EBOLA, inter alia. Among the evaluated compounds, inhibitors of the main protease of the coronavirus (Mpro) are becoming more and more promising candidates. Mpro holds a pivotal role during the onset of the infection and its function is intimately related with the beginning of viral replication. The interruption of its catalytic activity could represent a relevant strategy for the development of anti-coronavirus drugs. SARS-CoV-2 Mpro is a peculiar cysteine protease of the coronavirus family, responsible for the replication and infectivity of the parasite. This review offers a detailed analysis of the repurposed drugs and the newly synthesized molecules developed to date for the treatment of COVID-19 which share the common feature of targeting SARS-CoV-2 Mpro, as well as a brief overview of the main enzymatic and cell-based assays to efficaciously screen such compounds.

Recent Advances of Graphene-Based Strategies for Arsenic Remediation.

The decontamination of water containing toxic metals is a challenging problem, and in the last years many efforts have been undertaken to discover efficient, cost-effective, robust, and handy technology for the decontamination of downstream water without endangering human health. According to the World Health Organization (WHO), 180 million people in the world have been exposed to toxic levels of arsenic from potable water. To date, a variety of techniques has been developed to maintain the arsenic concentration in potable water below the limit recommended by WHO (10 µg/L). Recently, a series of technological advancements in water remediation has been obtained from the rapid development of nanotechnology-based strategies that provide a remarkable control over nanoparticle design, allowing the tailoring of their properties toward specific applications. Among the plethora of nanomaterials and nanostructures proposed in the remediation field, graphene-based materials (G), due to their unique physico-chemical properties, surface area, size, shape, ionic mobility, and mechanical flexibility, are proposed for the development of reliable tools for water decontamination treatments. Moreover, an emerging class of 3D carbon materials characterized by the intrinsic properties of G together with new interesting physicochemical properties, such as high porosity, low density, unique electrochemical performance, has been recently proposed for water decontamination. The main design criteria used to develop remediation nanotechnology-based strategies have been reviewed, and special attention has been reserved for the advances of magnetic G and for nanostructures employed in the fabrication of membrane filtration.

Design of naturally inspired jellyfish-shaped cyclopolylactides to manage osteosarcoma cancer stem cells fate.

We report the synthesis, characterization and biological profile of new bis-triazoled cyclopolylactides (c-PLA, c-PLA-FA, c-PLA-Rhod) obtained by an optimized combination of ROP and click chemistry reactions. Cyclo-PLA having a number average molecular weight of 6000 g mol-1 and a polydispersity index of 1.52 was synthetized by click ring-closure of well-defined α,ω-heterodifunctional linear precursors, followed by quaternarization of N3-triazole nodes, and subsequent CuAAC with azido-folate and azido-rhodamine yielding jellyfish-shaped c-PLA-FA and c-PLA-Rhod. Salinomycin (Sal) was loaded into jellyfish-shaped c-PLA-FA and c-PLA-Rhod nanoparticles (NPs) by nanoprecipitation, with a good encapsulation efficiency (79% and 84%, respectively) and loading content (7.1% and 7.6%, respectively). The biological studies focused on their antiproliferative effects on osteosarcoma bulk MG63 and cancer stem cells (CSCs). The cycloPLA-based NPs, with a size ranging between 125 and 385 nm, killed CSCs and MG63, with a higher efficacy on CSCs; they (unloaded or Sal-loaded) evoked on CSCs a cellular response similar to the payload, with a higher effect than the free Sal. Internalization studies indicated a fast cellular uptake (within 2 h) and sarcospheres remained fluorescent till 72 h. To the best of our knowledge, this is the first study reporting anti-CSCs properties of cycloPLA with jellyfish architecture and we believe could contribute to the development of effective strategies for osteosarcoma targeting.