Micelle encapsulation zinc-doped copper oxide nanocomposites reverse Olaparib resistance in ovarian cancer by disrupting homologous recombination repair.

Micelle Encapsulation Zinc-doped copper oxide nanocomposites (MEnZn-CuO NPs) is a novel doped metal nanomaterial prepared by our group based on Zinc doped copper oxide nanocomposites (Zn-CuO NPs) using non-micellar beam. Compared with Zn-CuO NPs, MEnZn-CuO NPs have uniform nanoproperties and high stability. In this study, we explored the anticancer effects of MEnZn-CuO NPs on human ovarian cancer cells. In addition to affecting cell proliferation, migration, apoptosis and autophagy, MEnZn-CuO NPs have a greater potential for clinical application by inducing HR repair defects in ovarian cancer cells in combination with poly (ADP-ribose) polymerase inhibitors for lethal effects.

Synthesis of Doped/Hybrid Carbon Dots and Their Biomedical Application.

Carbon dots (CDs) are a novel type of carbon-based nanomaterial that has gained considerable attention for their unique optical properties, including tunable fluorescence, stability against photobleaching and photoblinking, and strong fluorescence, which is attributed to a large number of organic functional groups (amino groups, hydroxyl, ketonic, ester, and carboxyl groups, etc.). In addition, they also demonstrate high stability and electron mobility. This article reviews the topic of doped CDs with organic and inorganic atoms and molecules. Such doping leads to their functionalization to obtain desired physical and chemical properties for biomedical applications. We have mainly highlighted modification techniques, including doping, polymer capping, surface functionalization, nanocomposite and core-shell structures, which are aimed at their applications to the biomedical field, such as bioimaging, bio-sensor applications, neuron tissue engineering, drug delivery and cancer therapy. Finally, we discuss the key challenges to be addressed, the future directions of research, and the possibilities of a complete hybrid format of CD-based materials.

Designing Natural Polymer-Based Capsules and Spheres for Biomedical Applications-A Review.

Natural polymers, such as polysaccharides and polypeptides, are potential candidates to serve as carriers of biomedical cargo. Natural polymer-based carriers, having a core-shell structural configuration, offer ample scope for introducing multifunctional capabilities and enable the simultaneous encapsulation of cargo materials of different physical and chemical properties for their targeted delivery and sustained and stimuli-responsive release. On the other hand, carriers with a porous matrix structure offer larger surface area and lower density, in order to serve as potential platforms for cell culture and tissue regeneration. This review explores the designing of micro- and nano-metric core-shell capsules and porous spheres, based on various functions. Synthesis approaches, mechanisms of formation, general- and function-specific characteristics, challenges, and future perspectives are discussed. Recent advances in protein-based carriers with a porous matrix structure and different core-shell configurations are also presented in detail.

Facile ultrasonic preparation of a polypyrrole membrane as an absorbent for efficient oil-water separation and as an antimicrobial agent.

Polypyrrole (PPY) spherical particles synthesized using carbon dots as an efficient catalyst were strongly embedded on fluorinated nonwoven fabric by ultrasonication to form a membrane with high hydrophilicity. An optimal amount of PPY adhered to the membrane after 30 min of sonication enhanced the overall membrane area with high hydrophilicity. Oil with high hydrophobicity was repelled by the resulting membrane, whereas water was freely penetrated and diffused from the membrane. The membrane exhibited good reusability and efficiency for the recovery of oil from a cooking oil-water mixture within 30 s. The incorporation of PPY in the fluorinated fabric imparts significant antibacterial properties against two common pathogens, Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). The anti-biofouling membrane could pave the way for its potential application to separate spilled oil from contaminated waters, comprising different microorganisms and living species. The novelty of this manuscript is described in a new system, the fabrication of PPY membranes with two important properties: biocidal and oil/water separation.

Immobilization of Heteroatom-Doped Carbon Dots onto Nonpolar Plastics for Antifogging, Antioxidant, and Food Monitoring Applications.

This work presents the facile synthesis of heteroatom-doped fluorescent carbon quantum dots (C-dots), which could serve as an antioxidant. Herein, nitrogen, phosphorous, and sulfur codoped carbon dots (NPSC-dots) have been synthesized by a single-step hydrothermal strategy. Owing to the radical scavenging activity of the NPSC-dots, they were tested against several methods as well as in practical applications. The antioxidant ability of the NPSC-dots was efficiently utilized on plastic films by coating with these NPSC-dots. For the very first time, NPSC-dots were immobilized onto nonpolar plastic films (polypropylene) via photochemical covalent grafting to extend the shelf life of food items or storage without affecting the quality of plastic films. The NPSC-dot-coated PP film with negligible deterioration of transparency was extensively studied using scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) analysis, X-ray photoelectron spectroscopy (XPS), contact angle measurement, and thermogravimetric analysis (TGA). The fluorescent character, antioxidant ability, and durability under different solvent systems of the coated film were examined. Also, the coated films were extensively and rigorously evaluated against simulated drastic environmental conditions to ensure the durability and antifogging application.

Exploring the Effect of Iron Metal-Organic Framework Particles in Polylactic Acid Membranes for the Azeotropic Separation of Organic/Organic Mixtures by Pervaporation.

A microporous carboxylate metal-organic framework MIL-100 Fe was prepared as submicron particles by microwave-assisted hydrothermal synthesis (Fe-MOF-MW). This product was explored, for the first time, for the preparation of polylactic acid (PLA) mixed matrix membranes. The produced MOF was characterised by powder X-ray diffraction (PXRD), environmental scanning electron microscopy (ESEM) as well as by thermogravimetric analysis (TGA) and nitrogen adsorption/desorption. The effect of different Fe-MOF-MW concentrations (0.1 and 0.5 wt%) on the membrane properties and performance were evaluated. These membranes were used in the pervaporation process for the separation of methanol/methyl tert-butyl-ether mixtures at the azeotropic point. The influence of the feed temperature and vacuum pressure on the membrane performance was evaluated and the results were compared with PLA pristine membranes. Moreover, the produced membranes have been characterised in terms of morphology, MOF dispersion in the polymeric membrane matrix, wettability, thickness, mechanical resistance and swelling propensity. The presence of Fe-MOF-MW was found to have a beneficial effect in improving the selectivity of mixed matrix membranes towards methanol at both concentrations. The highest selectivity was obtained for the PLA membranes embedded with 0.5 wt% of Fe-MOF-MW and tested at the temperature of 25 °C and vacuum pressure of 0.09 mbar.

Tailor made magnetic nanolights: fabrication to cancer theranostics applications.

Nanoparticles having magnetic and fluorescent properties could be considered as a gift to materials scientists due to their unique magneto-optical qualities. Multiple component particles can overcome challenges related with a single component and unveil bifunctional/multifunctional features that can enlarge their applications in diagnostic imaging agents and therapeutic delivery vehicles. Bifunctional nanoparticles that have both luminescent and magnetic features are termed as magnetic nanolights. Herein, we present recent progress of magneto-fluorescent nanoparticles (quantum dots based magnetic nanoparticles, Janus particles, and heterocrystalline fluorescent magnetic materials), comprehensively describing fabrication strategies, types, and biomedical applications. In this review, our aim is not only to encompass the preparation strategies of these special types of magneto-fluorescent nanomaterials but also their extensive applications in bioimaging techniques, cancer therapy (targeted and hyperthermic), and sustained release of active agents (drugs, proteins, antibodies, hormones, enzymes, growth factors).

In vitro copper oxide nanoparticle toxicity on intestinal barrier.

The use of CuO nanoparticles (NPs) has increased greatly and their potential effects on human health need to be investigated. Differentiated Caco-2 cells were treated from the apical (Ap) and the basolateral (Bl) compartment with different concentrations (0, 10, 50 and 100 µg/mL) of commercial or sonochemically synthesized (sono) CuO NPs. Sono NPs were prepared in ethanol (CuOe) or in water (CuOw), obtaining CuO NPs differing in size and shape. The effects on the Caco-2 cell barrier were assessed via transepithelial electrical resistance (TEER) evaluation just before and after 1, 2 and 24 hours of exposure and through the analysis of cytokine release and biomarkers of oxidative damage to proteins after 24 hours. Sono CuOe and CuOw NPs induced a TEER decrease with a dose-dependent pattern after Bl exposure. Conversely, TEER values were not affected by the Ap exposure to commercial CuO NPs and, concerning the Bl exposure, only the lowest concentration tested (10 µg/mL) caused a TEER decrease after 24 hours of exposure. An increased release of interleukin-8 was induced by sono CuO NPs after the Ap exposure to 100 µg/mL and by sono and commercial CuO after the Bl exposure to all the concentrations. No effects of commercial and sono CuO NPs on interleukin-6 (with the only exception of 100 µg/mL Bl commercial CuO) and tumor necrosis factor-α release were observed. Ap treatment with commercial and CuOw NPs was able to induce significant alterations on specific biomarkers of protein oxidative damage (protein sulfhydryl group oxidation and protein carbonylation).

Bifunctional Carbon Dots-Magnetic and Fluorescent Hybrid Nanoparticles for Diagnostic Applications.

There is a huge demand for materials capable of simple detection or separation after conjugation with specific biologic substances when applied as a diagnostic tools. Taking into account the photoluminescence properties of C-dots and the highly magnetic properties of Fe(0), a new hybrid composite of these components was synthesized via ultrasound irradiation. The material was fully characterized by various physicochemical techniques. The main goal of the current study was to obtain a highly magnetic and intense fluorescent hybrid material. The goal was achieved. In addition, magnetic particles tended to agglomerate. The new hybrid can be suspended in ethanol, which is an additional feature of the current research. The dispersion of the hybrid nanoparticles in ethanol was achieved by utilizing the interaction of iron particles with C-dots which were decorated with functional groups on their surface. The newly formed hybrid material has potential applications in diagnostic by conjugating with specific antibodies or with any other biologic compounds. Such application may be useful in detection of various diseases such as: cancer, tuberculosis, etc.

Antibacterial activities of microwave-assisted synthesized polypyrrole/chitosan and poly (pyrrole-N-(1-naphthyl) ethylenediamine) stimulated by C-dots.

Polypyrrole grafted with chitosan (PPy-g-CS) and poly (pyrrole-N-(1-naphthyl) ethylenediamine, a copolymer, (COP) have been synthesized by a one-step microwave procedure with carbon dots(C-Dots) as initiators. The electrostatic interaction between the positively charged polymers and negatively charged microbial cell membranes is widely anticipated to be responsible for cellular lysis. However, Escherichia coli exposed to PPy-g-CS (zeta potential = +46.9 mV) was completely perished after 3 h while COP (zeta potential = +64.1 mV) exhibited no antimicrobial effect. The two polymers were capable of eradicating Staphylococcus aureus, implying the charged effect is the main mechanism of cell death. The two polymers could also chelate calcium and other nutrients as well as form an external barrier to suppress the penetration of essential nutrients to support microbial survival and proliferation. In particular, pyrrole grafted chitosan was reasoned to stack onto the bacterial surface to impede the mass transfer and suppress the bacterial metabolic activity. The binding of chitosan to teichoic acids, essential acids of Gram-positive bacteria, would provoke a sequence of events and lead to bacterial death.

Antimicrobial Properties of Polyaniline and Polypyrrole Decorated with Zinc-Doped Copper Oxide Microparticles.

Polyaniline (PANI) and polypyrrole (PPY) were synthesized by carbon dots (CDs) under UV irradiation and then sonicated together with zinc acetate and copper acetate to form the PANI-Zn@CuO and PPY-Zn@Cu composites. The former consisted of agglomerated spherical particles with diameters of 1-5 µm, whereas the latter displayed irregular stick shapes with similar diameters. The bacterial potency of the composites against Escherichia coli and Staphylococcus aureus was enhanced remarkably with Zn doping in the CuO matrix, designated as Zn0.11Cu0.89O, at 0.144 mg/mL. The cell death was mainly attributed to the release of reactive oxygen species (ROS) that would severely damage DNA, proteins, and lipids. Bacteria could adhere to neutral surfaces of the composites by van der Waals attractive forces. The binding event disrupted the native surface charge of bacterial cells to induce cell lysis and result in eventual cell death.

A Short Report on the Polymerization of Pyrrole and Its Copolymers by Sonochemical Synthesis of Fluorescent Carbon Dots.

In polymer chemistry, polymerization constitutes the process of the conversion of monomers into polymers using an initiator to form polymeric chains. There are many polymerization techniques and different systems exist by which the polymers are classified. Recently, our group has reported the synthesis of polymers using both carbon dots (CDs) and UV light as initiators. In these reports, the carbon dots were used with or without UV light. The CDs produce free radicals in the presence of UV light, indicating their role as initiators. The CD surface has many unshared or unpaired electrons, making it negatively charged. The present study focuses on the use of CDs for the formation of polymers from monomers containing various functional group. The properties of the synthesized CDs and the polymers obtained from the various monomers were characterized by various analytical techniques, including Fourier-Transform Infrared (FTIR) spectroscopy, X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA) and Solid-State NMR spectroscopy. This polymerization technique is of interest both from the scientific aspect and for its applicative potential. The synthesized polymers were investigated for their various applications.

Antibacterial properties of polypyrrole-treated fabrics by ultrasound deposition.

Antimicrobial textiles can contribute to the fighting against antibiotic resistance pathogenic microorganisms. Polypyrrole is a conjugated polymer that exerts a biocidal action thanks to positive charges on its backbone chain produced during it synthesis. In this work, dispersions of stable polypyrrole nanoparticles were produced by chemical oxidative polymerization at room temperature in water. An ultrasound-assisted coating process was then used to effectively treat a polyester fabric with the nanoparticles to obtain an optimal antibacterial coating which efficiently eradicates the bacteria. The results showed that the treated fabric with about 4 g/m2 of polypyrrole had log bacteria reductions of 6.0 against Staphylococcus aureus and 7.5 against Escherichia coli. The combination of a polypyrrole synthesis in the form of water nanoparticles dispersions and a continuous coating of fabrics supported by ultrasound overcomes some issues of upscaling of the traditional in-situ chemical deposition used until now for the production of polypyrrole-coated textiles.

Zinc-Doped Copper Oxide Nanocomposites Inhibit the Growth of Pancreatic Cancer by Inducing Autophagy Through AMPK/mTOR Pathway.

Zinc doped copper oxide nanocomposites (Zn-CuO NPs) is a novel doped metal nanomaterial synthesized by our group using the sonochemical method. Our previous studies have shown that Zn-CuO NPs could inhibit cancer cell proliferation by inducing apoptosis via ROS-mediated pathway. In the present study, we studied the anticancer effect of Zn-CuO NPs on human pancreatic cancer cells. MTS assay revealed that Zn-CuO NPs was able to inhibit cancer cell growth. TEM, flow cytometry and fluorescence microscope analysis showed that Zn-CuO NPs induced autophagy significantly; the number of autophagosomes increased obviously in cells treated with Zn-CuO NPs. Western blot analysis revealed that treatment with the NPs resulted in activation of AMPK/mTOR pathway in both AsPC-1 and MIA Paca-2 cells in dose dependent manners. Moreover, in the presence of AMPK activator AMPKinone, the protein level of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I increased, while the protein expression of p-AMPK, p-ULK1, Beclin-1 and LC3-II/LC3-I decreased in the presence of AMPK inhibitor Compound C. In vivo study using xenograft mice revealed that Zn-CuO NPs significantly inhibited tumor growth with low toxicity. Our study confirms that Zn-CuO NPs inhibit the tumor growth both in vitro and in vivo for pancreatic cancer. AMPK/mTOR pathway plays an important role in the NPs induced inhibition of tumor growth.

Cytotoxic and proinflammatory responses induced by ZnO nanoparticles in in vitro intestinal barrier.

ZnO nanoparticles (NPs) are widely used nowadays, thus the gastrointestinal exposure to ZnO NPs is likely to be relevant and the effects on the intestinal barrier should be investigated. Polarized Caco-2 cells were exposed from the apical (Ap) and basolateral (Bl) compartments to increasing concentrations (0, 10, 50 and 100 µg/mL) of sonochemical (sono) and commercial ZnO NPs. The transepithelial electrical resistance (TEER), cell viability, proinflammatory cytokine release and presence of protein oxidative damage were evaluated after exposure. TEER was not significantly affected by Ap exposure to either sono or commercial ZnO NPs at any tested concentrations. After Bl exposure to sono ZnO NPs (all the concentrations) and to 100 µg/mL of commercial ZnO NPs TEER was decreased (P < 0.05). Ap and Bl exposure to 100 µg/mL sono ZnO NPs and Ap exposure to 50 µg/mL commercial ZnO NPs induced a significant (P < 0.05) release of interleukin-6. A significant (P < 0.05) release of interleukin-8 was observed after Ap exposure to ZnO NPs at 100 µg/mL and after Bl exposure to sono ZnO NPs at 100 µg/mL. Ap or Bl exposure to sono or commercial ZnO NPs did not affect tumour necrosis factor-alpha secretion or protein sulphydryl oxidation. In conclusion, the ZnO NP exposure from the Ap compartment appeared almost safe, while the exposure through the basal compartment appeared to be more hazardous and the different NP size and crystallinity seem to affect the mode of action, but further studies are necessary to elucidate better these toxicity mechanisms.

In vivo and in vitro study of a novel nanohydroxyapatite sonocoated scaffolds for enhanced bone regeneration.

There still remains a need for new methods of healing large bone defects, i.e., gaps in bone tissue that are too big to naturally heal. Bone regrowth scaffolds can fill the bone gap and enhance the bone regeneration by providing cells with a support to for new tissue formation. Coating of the scaffolds surface with nanocrystalline hydroxyapatite may enhance the osteoinductivity or osteoconductivity of such scaffolds. Here we present the sonocoating method to coat scaffolds with bioactive hydroxyapatite nanoparticles. We show a method, where the material to be coated is immersed in a colloidal suspension of nanoparticles with mean sizes of 10 nm and 43 nm in water, and high-power ultrasound waves are applied to the suspension for 15 min at 30 °C. High power ultrasounds lead to growth of cavitation bubbles in liquid, which implode at a critical size. The implosion energy propels the nanoparticles towards the material surface, causing their attachment to the scaffold. Using this technique, we produced a uniform layer of nanohydroxyapatite particles of thickness in the range 200 to 300 nm on two types of scaffolds: a porous ß-TCP ceramic scaffold and a 3D-printed scaffold made of PCL fibers. In vivo tests in rabbits confirmed that the novel coating strongly stimulated new bone tissue formation, with new bone tissue occupying 33% for the nHAP-coated PCL scaffold and 68% for the nHAP-coated ß-TCP after a 3-month test. The sonocoating method leads to formation of a bioactive layer on the scaffolds at temperature close to room temperature, very short time and in water. It is a green technological process, promising for bone tissue regeneration applications.

Zn-doped CuO nanocomposites inhibit tumor growth by NF-κB pathway cross-linked autophagy and apoptosis.

AIM: To investigate the antitumor effects and action mechanism of Zn-doped CuO nanocomposites (Zn-CuONPs). MATERIALS & METHODS: Therapeutic effects and mechanisms of Zn-CuONPs were investigated both in vitro and in vivo. RESULTS: Zn-CuONPs could inhibit tumor growth both in vitro and in vivo significantly. Zn-CuONPs treatment resulted in cytotoxicity, reactive oxygen species (ROS) production, DNA damage, apoptosis and autophagy. ROS scavenger N-acetylcysteine attenuated all of the above effects induced by Zn-CuONPs. N-acetylcysteine also restored the effects of Zn-CuONPs on protein expressions related to apoptosis, autophagy and NF-κB pathways. NF-κB pathway inhibitor pyrrolidine dithiocarbamate significantly attenuated Zn-CuONPs induced apoptosis and autophagy. CONCLUSION: Our data demonstrated that Zn-CuONPs could inhibit tumor growth both in vitro and in vivo by ROS-dependent apoptosis and autophagy cross-linked by NF-κB pathways.

Fluorescent metal-doped carbon dots for neuronal manipulations.

There is a growing need for biocompatible nanocomposites that may efficiently interact with biological tissues through multiple modalities. Carbon dots (CDs) could serve as biocompatible fluorescence nanomaterials for targeted tissue/cell imaging. Important goals toward this end are to enhance the fluorescence quantum yields of the CDs and to increase their targetability to cells. Here, sonochemistry was used to develop a one-pot synthesis of CDs, including metal-doped CDs (M@CDs), demonstrating how various experimental parameters, such as sonication time, temperature, and power of sonication affect the size of the CDs (2-10 nm) and their fluorescence properties. The highest measured quantum yield of emission was ∼16%. Similarly, we synthesized CDs doped with different metals (M@CDs) including Ga, Sn, Zn, Ag, and Au. The interaction of M@CDs with neuron-like cells was examined and showed efficient uptake and low cytotoxicity. Moreover, the influence of the M@CDs on the improvement of neurites during initiation and elongation growth phases were compared with pristine CDs. Our research demonstrates the use of M@CDs for imaging and for neuronal interactions. The M@CD nanocomposites are promising due to their biocompatibility, photo-stability and potential selective affinity, paving the way for multifunctional biomedical applications.

AS101-Loaded PLGA-PEG Nanoparticles for Autoimmune Regulation and Chemosensitization.

The in vivo delivery of therapeutic nanoparticles (NPs) represents a potentially powerful tool that can significantly alter the biological effects of pharmaceutically active compounds. Here, we report on sensitization of tumors to chemotherapy by ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) encapsulated in NPs, termed AS101-NPs, developed as a composite with the biocompatible and biodegradable copolymer of poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG). AS101 is a potent immunomodulating agent (both in vitro and in vivo) currently undergoing phase II clinical trials for antitumor activity and sensitization of tumors to chemotherapy. Approaches that can control the pharmacokinetic parameters to regulate its clearance from the administered drug delivery system and minimize side effects are of prodigious importance. A strategy to synthesize AS101-NPs by nanoprecipitation is presented, along with their physical characterization. The influence of AS101 encapsulation on its properties was evaluated in vivo. The AS101-NPs demonstrated a significantly enhanced peritoneal macrophage count compared with AS101 administered in vivo at a conventional dosage in mouse models. Moreover, AS101 inhibited B16 melanoma lung metastasis in mice when given intraperitoneally, before or after tumor cell inoculation. A bell-shaped dose-response was observed. The frequency of AS101 administration appears to be an important factor for achieving an optimal antimetastatic effect.

Zinc-doped copper oxide nanocomposites reverse temozolomide resistance in glioblastoma by inhibiting AKT and ERK1/2.

AIM: To assess the effect of zinc-doped copper oxide nanocomposites (nZn-CuO NPs) on glioblastoma therapy. MATERIALS & METHODS: nZn-CuO NPs were synthesized by sonochemical method and its antitumor effects and underlying molecular mechanisms were investigated both in vitro and in vivo. RESULTS: After nZn-CuO NPs treatment, cell proliferation was significantly inhibited in dividing cancer cells but less toxicity was observed in normal cells. In vivo studies show that nZn-CuO NPs inhibited tumor growth in a dose-dependent manner. Further study found that nZn-CuO NPs trigger cell reactive oxygen species (ROS) generation and intrinsic apoptotic pathway. In temozolomide resistance glioblastoma, nZn-CuO NPs disturb cell growth and sphere formation by inhibiting AKT and ERK1/2 activation. CONCLUSION: nZn-CuO NPs possess the potential to be developed as a novel anti-tumor agent, especially to treat temozolomide resistance glioblastoma.