Current Nanoscience - Volume 12, Issue 1, 2016

The blood–brain barrier (BBB) is a major obstacle to the effective delivery of therapeutic agents to the central nervous system (CNS). A small number of drugs have the potent ability to treat brain disease, but their efficiency is poor due to the existence of the BBB. Brain-targeted nanocarriers have been developed to overcome the BBB to increase drug accumulation in lesion regions in the brain and reduce toxicity in healthy brain tissue. Among these nanocarriers, stimuli-responsive nanocarriers (also known as smart nanocarriers) have become a hot topic in recent years. Stimuli-responsive nanocarriers can change their chemical structures or physical properties in response to environmental stimuli. When drugs or biomolecules are transported to certain regions of the brain, these changes can induce cargo release from the drug carrier to treat abnormal cells or tissues. These interesting characteristics provide us with an opportunity to endow various types of smart nanocarriers with the capability to response to single stimulus or multiple stimuli to release drugs at certain lesion regions. In current review, we describe the characteristics and function of the BBB and then focus on recent progress in stimuli-responsive nanocarriers targeting the brain. These naonocarriers include nanocarriers modified with pH-, redox-, photo- and enzyme-responsive polymers or band. We emphasize potential biological applications on brain diseases therapy of nanocarrier and their controlled release upon the application of different stimuli.

Cancers have become serious threat to human health and life, and they are critical to develop safe and effective theranostic methods for diagnosis and therapy of tumors. In recent years, real time cancer theranostic visualization systems (RT-CTVS) based on light-responsive nanoparticles have been developed. Especially, upconversion nanoparticles (UCNPs) have excellent optical properties and unique near-infrared (NIR) responsive. The minimized photodamage, low autofluorescence and high penetration depth can be achieved with UCNPs. Therefore, UCNPs are widely used in real time NIR mediated visualization systems of cancer diagnosis and therapy. In this review, we focus on the latest developments of rare earth ions doped upconversion fluorescence nanoparticles. First, the synthesis methods of UCNPs were briefly introduced. Second, the strategies of UCNPs surface modifications, including the ligand exchange, ligand oxidation, ligand interaction, ligand free synthesis, layer by layer growth and surface silanization were summarized. Third, the recent research progress in applying UCNPs to construct NIR light stimuli-responsive RT-CTVS, including imaging, drug delivery and photodynamic therapy (PDT) were highlighted. Finally, some of the current problems and future effort directions in these fields were also proposed.

The intrinsic structure and characteristics of polysaccharides make them suitable for forming stimuli-responsive nanosystems. Recently, a variety of polysaccharides have been applied to develop the sensitive nanomaterials for therapy, diagnosis and their combination. The mini-review intends to present the stimuli-responsive polysaccharides-based nanotheranostics through elucidating the typical examples of designing, preparing and applying the intelligent polysaccharides-based nanosystems published during the last five years. The relationship between the structure of polysaccharides and the function of the obtained nanosystems is discussed as well.

Background: Tumor tissues possess many unique features, including leaky vasculature and altered enzyme expression. An emerging field in anticancer drug delivery is to design enzyme-responsive nanoparticles, which may enable efficient accumulation in tumor tissues via the EPR effect and on demand release of the drug in response to enzymes. Many strategies were proposed to promote the development of efficient enzyme-responsive nanoparticles. Methods: In this review, we highlighted nanoparticle systems that can unload their cargo in response to a specific enzymatic stimulus, especially tumor-associated enzymes that have been harnessed in drug delivery. Current challenges and future directions were proposed for the development of better drug delivery systems. Results: Many challenges remain before a clinically useful formulation can be developed. The biocompatibility and biodegradability of the nanocarriers have to be taken into consideration. The presence and potency of disease related enzymes should be fully understood as enzyme activities may vary dramatically in different diseases, patients, or even at different disease stages. Deliberate explorations should be concerned on the design of enzyme specific linkages and substrates as many enzyme families and subtypes may share similar cleave sites. Conclusion: Successful drug delivery systems must be able to overcome several physiological barriers and release the drug cargo at the target site. An emerging field to achieve this goal is enzyme responsive nanoparticles, which offer a meaningful way to control drug release purposefully. Great advancement has been made by utilizing a variety of combinations of nanoparticles and enzymes. There are many kinds of enzymes available for enzyme-responsive drug delivery, the key point is to realize enzyme-stimulated degradation of nanocarriers or cleavage of drugs as well as drug release in a controlled manner, even though there are many types of nanocarriers in nanomedicine. By incorporating enzyme labile linkages, liposomes, polymeric nanoparticles, and inorganic particles are all capable of being engineered to release the encapsulated drug on demand, which holds great potential in reducing the exposure to non-diseased tissue, cell, and even subcellular organelles.

Cancer remains the second leading cause of death worldwide even though advances in early diagnosis and treatment are being actively pursued. Nanoparticles (NPs) are one of the most widely studied materials in the recent decade and are emerging as promising agents in the cancer management. Pertinent to realizing this truth, toxicity issues related to nanoproducts are of particular concern that is often ignored. Nanostructures synthesised using materials of biological origin using eco-friendly ‘green’ chemistry approach, partially addresses this problem. Biologically synthesised NPs are accounted for various applications in cancer management such as bioimaging, drug delivery, sensitising, photothermal and photodynamic therapy and so on. Cancer stem cells (CSCs) are a small population of extremely tumourigenic and intrinsically drug resistant cells that are responsible for the tumour initiation, progression, resistance, and relapse. In addition to small molecules and nucleic acid-based therapeutics, combining nanomaterials with antibodies against CSC-specific markers or CSC-targeting agents have been engaged for the selective targeting and developing of anti-CSCs therapeutics. Yet despite the benefits reaped by the NPs, in the overall management of complex diseases like cancer, disadvantages such as toxicity and pollution inevitably follow. The first part of this review essentially budges on the application of NPs produced using ‘green’ biological materials, which are poised to dissipate some of the issues. The latter half is aimed to discuss the utility of nanoparticles in CSC-targeted therapies.

Background: Inflammation is an immune response that indicates several pathophysiological conditions, including pathogen infection, tissue injury, and tumor growth, in human diseases. During the processes of infection, tumor growth and autoimmune responses, tissue-associated macrophages distributed in the body play a central role in the onset of inflammation and are actively involved in maintaining homeostasis. Objective: Because the role of macrophages in diseases such as infectious diseases, chronic inflammatory diseases, and cancer are now well understood, strategies to target macrophages in uncontrollable diseases are of growing importance. The application of nanotechnology and nanoscience-based approaches for the treatment, diagnosis, monitoring, and control of biological systems has recently been referred to as “nanomedicine”. Nanoparticles not only are efficient for the delivery of therapeutic drugs and for imaging but also potentially facilitate cell activation and ablation. Certain unique types of nanoparticles naturally target cells of the mononuclear phagocyte system (MPS), and particularly macrophages. Results: This natural targeting capacity can be used for application in drug delivery and diagnosis. Controlling nanoparticles’ physicochemical properties, including size, charge, and composition, has emerged as a favored approach to target macrophages to achieve high endocytic activity. Ligand-receptor strategies for nanoparticle targeting to macrophages have been explored, including peptide, antibody, and lectin coating to specifically target drug-loaded nanoparticles to specific receptor types expressed on macrophages. Conclusion: This mini-review highlights rational approaches to the design and surface engineering of nanoparticles. Approaches to site-specific drug delivery and medical imaging for the treatment and diagnosis of macrophage-related human diseases are also discussed. Finally, recent nanotechnology-based approaches to devising macrophage-specific targeted therapy are highlighted.

Porous microspheres of casein/amorphous calcium phosphate nanocomposite are prepared using casein sodium salt, CaCl2, Na2HPO4•12H2O and Na2HPO4•12H2O in aqueous solution at room temperature. The effects of experimental parameters such as solution pH, casein sodium salt and ageing time on the product are investigated. Porous microspheres of casein/amorphous calcium phosphate nanocomposite are characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, thermogravimetric (TG) analysis, and Brunauer-Emmett-Teller (BET) specific surface area and pore size distribution. The as-prepared porous microspheres of casein/amorphous calcium phosphate nanocomposite are favorable for drug loading and release using ibuprofen (IBU), docetaxel (Dtxl) and vitamin B5 (B5) as typical drugs, and show low cytotoxicity in the cytotoxicity test. Thus, porous microspheres of casein/amorphous calcium phosphate nanocomposite have promising applications in various biomedical fields such as drug delivery.

Background: As lamellar clay, montmorillonite (MMT) has intercalation, swelling, and ion exchange properties. Silver nanoparticles were prepared using the chemical reducing method in montmorillonite as a solid support at room temperature. The biological approaches for synthesis of nanoparticles are better than chemical and physical procedures because of low energy and time expenditure, non toxic solvents and non dangerous material for environment. Methods: In this work, green biosynthesis of silver-montmorillonite (MMT) nanocomposite is reported at room temperature, using water extract of Ziziphora tenuior L as reducing agent into the interlamellar space of MMT. Results: The synthesized silver-montmorillonite (Ag/MMT) nanocomposite were characterized using ultraviolet-visible spectroscopy (UV-Vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and powder Xray diffraction (XRD). The UV-Vis spectra of the Silver-montmorillonite nanocomposite showed absorption peak at around 415 nm. SEM, XRD and TEM studies showed that the average particles size of Ag/MMT nanocomposite were about 21.79 nm and also XRD patterns indicated that the structure of the nanocomposite is face-centered cubic. Conclusion: The results showed, green synthesis of silver-montmorillonite nanocomposite was have successfully carried out from the AgNO3/MMT suspension using water extract of Ziziphora tenuior L at room temperature. The XRD pattern showed that the silver-montmorillonite nanocomposite formed were crystalline in nature. Also The SEM and TEM results showed that spherical silver nanoparticles and average particles size were about 21.79 nm.

Background: Poor specific energy density of carbon material limits it as promising candidate for being used in two electrode system. This problem can be overcome by employing pseudocapacitive materials such as metal oxides/hydroxides and conducting polymers with carbon materials in two electrode device. In this study, PANI containing composite electrodes based on carbon cloths and felts with high specific surface area have been developed for symmetric supercapacitor device by one step chemical polymerization of aniline. Methods: Polyaniline (PANI) based composites have been prepared with various carbon materials (Carbopon B-Active, Felt 228, cloth Busofit T-040 and Busofit T-040/Carbopon B-Active (C/C Composite) by chemical polymerization of aniline in an acidic medium. Ammonium persulfate is used as an oxidizing agent. The potential for using these Carbon materials/ Polyaniline composites (CMs/PANI composites) as supercapacitor electrodes have been explored by cyclic voltammetry and galvanostatic charge/discharge tests within a potential window of 0- 1.0 V in 6M H2SO4 aqueous electrolyte. Results: Based on the charge/discharge test, it is found that the highest specific capacitance could be achieved from the composite with 25 wt. % PANI. CMs/PANI composites demonstrate significant capacitance enhancement in comparison to CMs. Conclusion: PANI-containing composites based on commercially available carbon felts Carbopon B-Active, Felt 228, carbon cloth Busofit T-040 and carbon/carbon composite “Busofit T-040/Carbopon B-Active” have been prepared. It has been shown that the CMs/PANI composites have a capacity of 1.3-2.2 times higher than the capacity of unmodified CMs. The coulombic efficiency of composites has been measured to be about 97-99%. This encouraging result demonstrates the importance of developed CMs/PNI composites as binder free and flexible electrode materials for high energy symmetric supercapacitor.

Background: Chemical methods for reducing the silver ions may have incompatible effects in medical applications, so the synthesis of nanoparticles using microorganisms and plants extract may help to solve this problem. Therefore biological approaches for synthesis of nanoparticles are better than chemical and physical procedures because of low energy and time expenditure, non toxic solvents and non dangerous material for environment. Methods: Bio-synthesis of silver nanoparticles (Ag NPs) using water extract of Satureja hortensis L is carried out successfully at room temperature. Results: TEM study showed that mean diameter and standard deviation for the formation of silver nanoparticles were 15±7.402 nm. The antibacterial effects of silver nanoparticles on Gram positive and Gram negative bacteria were also performed. Conclusion: It can be concluded that silver nanoparticles were synthesized with an average size of 15±7.402 nm and spherical in shape, using the water extract of Satureja hortensis L at room temperature. silver nanoparticles by UVVisible, SEM, TEM and XRD were characterized. Synthesis of silver nanoparticles using plant like Satureja hortensis L is a better alternative to chemical synthesis. The green synthesis of nanoparticles is an eco-friendly method because of the usage of natural products. Also study found that the Ag/Satureja hortensis L shows antibacterial activity on both Gram positive and Gram negative bacteria.

Background: Graphene, a single atom thickness two dimensional material, has been considered as a promising material in nanoscience and nanotechnology due to its extraordinary optical, electronic, catalytic and mechanical properties. Green synthesis of graphene is of importance because of its low cost, simplicity in preparation and its aqueous dispersibility. The present work describes the use of T. bellirica fruit (pericarp) aqueous extracts as green reducing and stabilizing agent for graphene synthesis from graphene oxide (GO). Further, the prepared graphene was characterized by using different spectroscopic and microscopic techniques. Finally, the manuscript describes the possible mechanism for the stabilization of graphene by the plant polyphenols. Methods: GO was prepared by following a modified Hummers method. Reduced graphene oxide (RGO) was prepared from GO using T. bellirica (pericarp) aqueous extracts. Further, the synthesized RGO was characterized using UVVisible, XRD, SEM, TEM and FTIR techniques. Results: The prepared T. bellirica reduced graphene oxide (TBG) was characterized by using various instrumental techniques. UV-Visible and XRD have indicated conversion of GO to RGO. SEM and HR-TEM images have showed the thin, transparent and silk like appearance of TBG. Further, FTIR analysis has represented the participation of polyphenolic hydroxyl groups of T. bellirica extract in the reduction of GO to RGO and subsequent stabilization of RGO by oxidised polyphenols via π-π stacking interactions. Additionally, the band gap of TBG was calculated as 3.75 eV by DRS analysis. Conclusion: This work has shown a facile, low-cost, ecofriendly synthetic method for the production of reduced graphene oxide by using polyphenols from T. bellirica fruit extracts. FTIR analysis has concluded that the naturally occurring polyphenols present in T. bellirica extract are responsible for the reduction and stabilization of TBG. This paper further shows an eco-friendly method to produce RGO in bulk scale by using low cost polyphenols rich plant extracts.

Background: Pectin is a natural hetero-polysaccharide found in some fruits and vegetables with good biocompatibility and biodegradability. Besides the inherent functions of pectin in plants and its normal applications as gelling and thickening agents in food industry, pectin-based nanomaterials have attracted great attention owing to their unique properties such as the high specific surface area compared to the bulk pectin. Pectin-based nanomaterials combine the advantages of both pectin and the nanoscaled particles so that they show great potential in some other fields. Methods: Recent advance of pectin-based nanomaterials is reviewed including their synthesis strategies and applications. Results: At present, common methods based on nanoemulsion technique, ionotropic gelation, redox reactions and so on have been reported for the synthesis of pectin nanomaterials and pectin stabilized/capped nanomaterials. And these pectinbased nanomaterials can be used as gene/drug delivery system, antimicrobial agents and adsorbents for metal ions and dyes in wastewater treatment. Conclusion: The variety of nanoparticles is increasing and their applications are wider, so there are still more possibilities for us to investigate the pectin-based nanomaterials including the synthesis methods and applications in other fields. For example, the synthesis of fluorescent pectin-based nanoparticles and their applications in sensing and bioimaging. Using the advantages of both pectin and nanomaterials, we hope more pectin-based nanomaterials can be designed and synthesized and further applied in desired areas.

Background: The drugs used for treating multi drug resistant tuberculosis (MDR-TB) are extremely toxic, expensive and less potent with limited sterilizing activity. With the emergence of several drug resistant strains of tuberculosis there is a pressing need for new drug development. In the current study, clinically used anti-infective antibiotics such as moxifloxacin (MOX), econazole (ECZ) and ethionamide (ETH) were encapsulated in poly-(lactide-co-glycolide) nanoaprticles and evaluated for their therapeutic efficacy in a MDR-TB infected mouse model. It is envisaged that such formulations would improve patient compliance and reduction in the number of dosages. Methods: Moxifloxacin and ethionamide nanoparticles were prepared by multiple emulsion and solvent evaporation method while econazole nanoparticles were prepared by nanopreciptitation method. Mice were aerosol infected with MDR-TB JAL11050 and treated with free drugs and drugs encapsulated in PLGA nanoparticles. The lungs and spleen were evaluated for reduction in bacterial load (colony forming units, CFU) and histopathological studies. Results: Moxifloxacin, econazole and ethionamide were encapsulated with high efficiency in PLGA nanoparticles. Eight weeks of oral administration of individual nanoformulations (PLGA-NP-ECZ / PLGA-NP-MOX / PLGA-NP-ETH) showed limited reduction of CFUs in lungs and spleen while with 8 doses of a combination of the three nanoformulations (PLGA- NP- ECZ+PLGA-NPMOX+PLGA-NP-ETH) there was a significant reduction in CFUs in lungs as well as in spleen. Corroborating the results with histopathology revealed that the combination of 3-drugs loaded nanoparticles decreased the congestion in the lungs to 50%. Conclusion: Chemotherapy of MDR-TB infected mice with weekly doses of 3-drugs nanoformulations (PLGA-NPECZ+ PLGA-NP-MOX+PLGA-NP-ETH) led to the clearance of bacilli from lungs and the spleen. This is a first report on the potential efficacy of a combination of ECZ, MOX and ETH nanoparticles against MDR-TB.

Background: Surface microstructure of cancerous cell is particularly vital since cell constantly changes its shape as interacting with extracellular matrix and neighboring cells. Atomic force microscope (AFM) has an unparalleled excellence in surface profiling of cells while the scanning quality depends upon experience or experiment conditions primarily. Methods: In this paper, a quadratic regression orthogonal rotation combination design was conducted to obtain optimal parameters of cell scanning via AFM. Results: By iterative calculation, the optimum AFM scanning of cell can be achieved at setpoint of 0.61 V, scanning rate of 2.23 Hz and proportional gain of 3.85. Satisfactory surface morphology images of human bronchial epithelium BEAS- 2B were acquired at this calculated scanning condition, in which the details of surface micro cilia structure and the pore structure are visible. Conclusion: Thus AFM is an effective means for real-time visualization of cell topography in liquid environment and this emerging insight into these cell profiling may promote the understanding of the underlying mechanism for cellular inner reconstruction and cell migration.

Background: Excessive consumption of synthetic dyes in various industrial processes leads to the production of a considerable amount of wastewater polluted with these chemicals. Therefore, the discharge of wastewater containing these chemicals with stable structures into natural streams reduces light penetration, and accordingly affects photosynthetic phenomena, and increases toxicity and chemical oxygen demand. Thus treatment of industry wastewater containing dyes prior to discharge is of paramount importance. In this study, the nanostructured magnetite, which treated using effective and cheap nitrogen plasma, was used as the iron source in sonocatalytic process to degrade Basic Blue 3 (BB3) dye in aqueous solutions. Methods: Magnetite particles placed in plasma rector under low pressure N2 atmosphere. DC high-voltage was applied on electrodes to generate glow discharge plasma. Then, the magnetite nanostructures were obtained and collected for using as catalyst in sonocatalytic reaction for decolorization of BB3 solution. Sonocatalytic experiments with PTM were carried out in a 250-mL erlenmeyer immersed into the ultrasonic batch. Typically, 100 mL BB3 solution with appropriate quantity of plasma-treated magnetite (PTM) was added to the erlenmeyer. Throughout the experiments, about 5 mL of the solution was withdrawn from the erlenmeyer at specific time intervals to determine concentration of BB3 in solutions by photometrically using UV–Vis spectrophotometer. Results: The results show that the BB3 degradation efficiency was 61%, and 98% at 90 min in the ultrasonic, and sonocatalytic reaction, respectively. The highest decolorization efficiency was achieved at an initial pH of 3 in the presence of 0.75 g/L PTM. Integrated gas chromatography–mass spectrometry showed five intermediate compounds that were identified with high match factor of mass spectrum. Conclusion: Plasma technique is an appropriate treatment method to decrease the size of natural magnetite, and to enhance the catalytic ability of this compound in the sonocatalytic process. The catalytic performance of PTM was dependent on the initial dye concentration, ultrasonic power density, pH, and catalyst dosage. The PTM dose, as predicts by ANN model with a relative importance of 31.08 %, appeared to be the most effective parameter in this process.