Cancer is a leading cause of death worldwide. Several classes of drugs are available to treat different types of cancer. Currently, researchers are paying significant attention to the development of drugs at the nanoscale level to increase their target specificity and to reduce their concentrations. Nanotechnology is a promising and growing field with multiple subdisciplines, such as nanostructures, nanomaterials, and nanoparticles. These materials have gained prominence in science due to their size, shape, and potential efficacy. Nanomedicine is an important field involving the use of various types of nanoparticles to treat cancer and cancerous cells. Synthesis of nanoparticles targeting biological pathways has become tremendously prominent due to the higher efficacy and fewer side effects of nanodrugs compared to other commercial cancer drugs. In this review, different medicinal plants and their active compounds, as well as green-synthesized metallic nanoparticles from medicinal plants, are discussed in relation to their anticancer activities.
Matched MeSH terms: Metal Nanoparticles/therapeutic use*; Metal Nanoparticles/chemistry
Very narrow and pure silver nanoparticles were synthesized by modified thermal treatment method via oxygen and nitrogen flow in succession. The structural and optical properties of the calcined silver nanoparticles at 600°C with diverse Poly(vinylpyrrolidone) concentrations varied from 2% to 4% were studied by means of different techniques. Fourier transform infrared spectroscopy was used to monitor the production of pure Ag nanoparticles at a given Poly(vinylpyrrolidone) concentration. The X-ray powder diffraction spectra are evidence for the transformation of the amorphous sample at 30°C to the cubic crystalline nanostructures at the calcination temperatures for all Poly(vinylpyrrolidone) concentrations. The transmission electron microscopy images showed the creation of spherical silver nanoparticles with the average particle size decreased by increasing Poly(vinylpyrrolidone) concentrations from 4.61 nm at 2% to 2.49 nm at 4% Poly(vinylpyrrolidone). The optical properties were investigated by means of UV-vis absorption spectrophotometer, which showed an increase in the conduction band of Ag nanoparticles with increasing Poly(vinylpyrrolidone) concentrations from 2.83 eV at 2% Poly(vinylpyrrolidone) to 2.94 eV at 4% Poly(vinylpyrrolidone) due to decreasing particle size. This was due to less attraction between conduction electrons and metal ions for smaller particle size corresponding to fewer atoms that made up the metal nanoparticles.
Matched MeSH terms: Metal Nanoparticles/ultrastructure; Metal Nanoparticles/chemistry*
Targeting the small intestine employing nanotechnology has proved to be a more effective way for site-specific drug delivery. The drug targeting to the small intestine can be achieved via nanoparticles for its optimum bioavailability within the systemic circulation. The small intestine is a remarkable candidate for localized drug delivery. The intestine has its unique properties. It has a less harsh environment than the stomach, provides comparatively more retention time, and possesses a greater surface area than other parts of the gastrointestinal tract. This review focuses on elaborating the intestinal barriers and approaches to overcome these barriers for internalizing nanoparticles and adopting different cellular trafficking pathways. We have discussed various factors that contribute to nanocarriers' cellular uptake, including their surface chemistry, surface morphology, and functionalization of nanoparticles. Furthermore, the fate of nanoparticles after their uptake at cellular and subcellular levels is also briefly explained. Finally, we have delineated the strategies that are adopted to determine the cytotoxicity of nanoparticles.
Silver nanoparticles (Ag-NPs) were synthesized into the interlamellar space of montmorillonite (MMT) by using the γ-irradiation technique in the absence of any reducing agent or heat treatment. Silver nitrate and γ-irradiation were used as the silver precursor and physical reducing agent in MMT as a solid support. The MMT was suspended in the aqueous AgNO(3) solution, and after the absorption of silver ions, Ag(+) was reduced using the γ-irradiation technique. The properties of Ag/MMT nanocomposites and the diameters of Ag-NPs were studied as a function of γ-irradiation doses. The interlamellar space limited particle growth (d-spacing [d(s)] = 1.24-1.42 nm); powder X-ray diffraction and transmission electron microscopy (TEM) measurements showed the production of face-centered cubic Ag-NPs with a mean diameter of about 21.57-30.63 nm. Scanning electron microscopy images indicated that there were structure changes between the initial MMT and Ag/MMT nanocomposites under the increased doses of γ-irradiation. Furthermore, energy dispersive X-ray fluorescence spectra for the MMT and Ag/ MMT nanocomposites confirmed the presence of elemental compounds in MMT and Ag-NPs. The results from ultraviolet-visible spectroscopy and TEM demonstrated that increasing the γ-irradiation dose enhanced the concentration of Ag-NPs. In addition, the particle size of the Ag-NPs gradually increased from 1 to 20 kGy. When the γ-irradiation dose increased from 20 to 40 kGy, the particle diameters decreased suddenly as a result of the induced fragmentation of Ag-NPs. Thus, Fourier transform infrared spectroscopy suggested that the interactions between Ag-NPs with the surface of MMT were weak due to the presence of van der Waals interactions. The synthesized Ag/MMT suspension was found to be stable over a long period of time (ie, more than 3 months) without any sign of precipitation.
Matched MeSH terms: Metal Nanoparticles/radiation effects; Metal Nanoparticles/chemistry*
Type 2 diabetes mellitus (T2DM) is a major chronic disease that is prevalent worldwide, and it is characterized by an increase in blood glucose, disturbances in the metabolism, and alteration in insulin secretion. Nowadays, food-based therapy has become an important treatment mode for type 2 diabetes, and phytobioactive compounds have gained an increasing amount of attention to this end because they have an effect on multiple biological functions, including the sustained secretion of insulin and regeneration of pancreatic islets cells. However, the poor solubility and lower permeability of these phyto products results in a loss of bioactivity during processing and oral delivery, leading to a significant reduction in the bioavailability of phytobioactive compounds to treat T2DM. Recently, nanotechnological systems have been developed for use as various types of carrier systems to improve the delivery of bioactive compounds and thus obtain a greater bioavailability. Furthermore, carrier systems in most nanodelivery systems are highly biocompatible, with nonimmunologic behavior, a high degree of biodegradability, and greater mucoadhesive strength. Therefore, this review focuses on the various types of nanodelivery systems that can be used for phytobioactive compounds in treating T2DM with greater antidiabetic effects. There is also additional focus on improving the effects of various phytobioactive compounds through nanotechnological delivery to ensure a highly efficient treatment of type 2 diabetes.
Silver nanoparticles (Ag NPs) are invested in various sectors and are becoming more persistent in our ambient environment with potential risk on our health and the ecosystems. The current study aims to investigate the histological, histochemical and ultrastructural hepatic changes that might be induced by 10 nm silver nanomaterials. Male mice (BALB/C) were exposed for 35 injections of daily dose of 10 nm Ag NPs (2 mg/kg). Liver tissues were subjected to examination by light and electron microscopy for histological, histochemical and ultrastructural alterations. Exposure to Ag NPs induced Kupffer cells hyperplasia, sinusoidal dilatation, apoptosis, ground glass hepatocytes appearance, nuclear changes, inflammatory cells infiltration, hepatocytes degeneration and necrosis. In addition, 10 nm Ag NPs induced histochemical alterations mainly glycogen depletion with no hemosiderin precipitation. Moreover, these nanomaterials exhibited ultrastructure alterations including mitochondrial swelling and cristolysis, cytoplasmic vacuolation, apoptosis, multilammellar myelin figures formation and endoplasmic destruction and reduction. The findings revealed that Ag NPs can induce alterations in the hepatic tissues, the chemical components of the hepatocytes and in the ultrastructure of the liver. One may also conclude that small size Ag NPs, which are increasingly used in human products could cause various toxigenic responses to all hepatic tissue components.
Matched MeSH terms: Metal Nanoparticles/toxicity*; Metal Nanoparticles/chemistry
Existing nonviral gene delivery systems to lungs are inefficient and associated with dose limiting toxicity in mammalian cells. Therefore, carbonate apatite (CO3Ap) nanoparticles were examined as an alternative strategy for effective gene delivery to the lungs. This study aimed to (1) assess the gene delivery efficiency of CO3Ap in vitro and in mouse lungs, (2) evaluate the cytotoxicity effect of CO3Ap/pDNA in vitro, and (3) characterize the CO3Ap/pDNA complex formulations. A significantly high level of reporter gene expression was detected from the lung cell line transfected with CO3Ap/pDNA complex prepared in both serum and serum-free medium. Cytotoxicity analysis revealed that the percentage of the viable cells treated with CO3Ap to be almost similar to the untreated cells. Characterization analyses showed that the CO3Ap/pDNA complexes are in a nanometer range with aggregated spherical structures and tended to be more negatively charged. In the lung of mice, highest level of transgene expression was observed when CO3Ap (8 μL) was complexed with 40 μg of pDNA at day 1 after administration. Although massive reduction of gene expression was seen beyond day 1 post administration, the level of expression remained significant throughout the study period.
A novel porous three-dimensional bone scaffold was developed using a natural polymer (alginate/Alg) in combination with a naturally obtained biomineral (nano cockle shell powder/nCP) through lyophilization techniques. The scaffold was developed in varying composition mixture of Alg-nCP and characterized using various evaluation techniques as well as preliminary in vitro studies on MG63 human osteoblast cells. Morphological observations using SEM revealed variations in structures with the use of different Alg-nCP composition ratios. All the developed scaffolds showed a porous structure with pore sizes ideal for facilitating new bone growth; however, not all combination mixtures showed subsequent favorable characteristics to be used for biological applications. Scaffolds produced using the combination mixture of 40% Alg and 60% nCP produced significantly promising results in terms of mechanical strength, degradation rate, and increased cell proliferation rates making it potentially the optimum composition mixture of Alg-nCP with future application prospects.
In the present work, nanohybrid of an anticancer drug, doxorubicin (Dox) loaded gold-coated superparamagnetic iron oxide nanoparticles (SPIONs@Au) were prepared for a combination therapy of cancer by means of both hyperthermia and drug delivery. The Dox molecules were conjugated to SPIONs@Au nanoparticles with the help of cysteamine (Cyst) as a non-covalent space linker and the Dox loading efficiency was investigated to be as high as 0.32 mg/mg. Thus synthesized particles were characterized by HRTEM, UV-Vis, FT-IR, SQUID magnetic studies and further tested for heat and drug release at low frequency oscillatory magnetic fields. The hyperthermia studies investigated to be strongly influenced by the applied frequency and the solvents used. The Dox delivery studies indicated that the drug release efficacy is strongly improved by maintaining the acidic pH conditions and the oscillatory magnetic fields, i.e. an enhancement in the Dox release was observed from the oscillation of particles due to the applied frequency, and is not effected by heating of the solution. Finally, the in vitro cell viability and proliferation studies were conducted using two different immortalized cell lines containing a cancerous (MCF-7 breast cancer) and non-cancerous H9c2 cardiac cell type.
The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO₃/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO₃/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO₃/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO₃ nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.
The preparation of magnetic nanoparticles coated with chitosan-prindopril erbumine was accomplished and confirmed by X-ray diffraction, TEM, magnetic measurements, thermal analysis and infrared spectroscopic studies. X-ray diffraction and TEM results demonstrated that the magnetic nanoparticles were pure iron oxide phase, having a spherical shape with a mean diameter of 6 nm, compared to 15 nm after coating with chitosan-prindopril erbumine (FCPE). Fourier transform infrared spectroscopy study shows that the coating of iron oxide nanoparticles takes place due to the presence of some bands that were emerging after the coating process, which belong to the prindopril erbumine (PE). The thermal stability of the PE in an FCPE nanocomposite was remarkably enhanced. The release study showed that around 89% of PE could be released within about 93 hours by a phosphate buffer solution at pH 7.4, which was found to be of sustained manner governed by first order kinetic. Compared to the control (untreated), cell viability study in 3T3 cells at 72 h post exposure to both the nanoparticles and the pure drug was found to be sustained above 80% using different doses.
Iron oxide magnetic nanoparticles (MNPs) were synthesized by the coprecipitation of iron salts in sodium hydroxide followed by coating separately with chitosan (CS) and polyethylene glycol (PEG) to form CS-MNPs and PEG-MNPs nanoparticles, respectively. They were then loaded with kojic acid (KA), a pharmacologically bioactive natural compound, to form KA-CS-MNPs and KA-PEG-MNPs nanocomposites, respectively. The MNPs and their nanocomposites were characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, vibrating sample magnetometry, and scanning electron microscopy. The powder X-ray diffraction data suggest that all formulations consisted of highly crystalline, pure magnetite Fe3O4. The Fourier transform infrared spectroscopy and thermogravimetric analysis confirmed the presence of both polymers and KA in the nanocomposites. Magnetization curves showed that both nanocomposites (KA-CS-MNPs and KA-PEG-MNPs) were superparamagnetic with saturation magnetizations of 8.1 emu/g and 26.4 emu/g, respectively. The KA drug loading was estimated using ultraviolet-visible spectroscopy, which gave a loading of 12.2% and 8.3% for the KA-CS-MNPs and KA-PEG-MNPs nanocomposites, respectively. The release profile of the KA from the nanocomposites followed a pseudo second-order kinetic model. The agar diffusion test was performed to evaluate the antimicrobial activity for both KA-CS-MNPs and KA-PEG-MNPs nanocomposites against a number of microorganisms using two Gram-positive (methicillin-resistant Staphylococcus aureus and Bacillus subtilis) and one Gram-negative (Salmonella enterica) species, and showed some antibacterial activity, which could be enhanced in future studies by optimizing drug loading. This study provided evidence for the promise for the further investigation of the possible beneficial biological activities of KA and both KA-CS-MNPs and KA-PEG-MNPs nanocomposites in nanopharmaceutical applications.
Silver nanoparticles (Ag-NPs) were successfully synthesized using the UV irradiation of aqueous solutions containing AgNO(3) and gelatin as a silver source and stabilizer, respectively. The UV irradiation times influence the particles' diameter of the Ag-NPs, as evidenced from surface plasmon resonance (SPR) bands and transmission electron microscopy (TEM) images. When the UV irradiation time was increased, the mean size of particles continuously decreased as a result of photoinduced Ag-NPs fragmentation. Based on X-ray diffraction (XRD), the UV-irradiated Ag-NPs were a face-centered cubic (fcc) single crystal without any impurity. This study reveals that the UV irradiation-mediated method is a green chemistry and promising route for the synthesis of stable Ag-NPs for several applications (e.g., medical and surgical devices). The important advantages of this method are that it is cheap, easy, and free of toxic materials.
Matched MeSH terms: Metal Nanoparticles/ultrastructure; Metal Nanoparticles/chemistry*
In the present study, we investigate the mucoadhesive characteristics and release of the anticancer agent curcumin, contained in chitosan nanoparticles (CS-NPs). Such a system has potential therapeutic benefits in the treatment of colon cancer through prolonged retention and delivery. The CS-NPs were ionically gelled with tripolyphosphate (TPP) and registered an isoelectric pH of 6.2 (z-average diameter of 214 nm ± 1.0 nm). pH variations around the isoelectric point caused a reduction in CS-NPs electrical charge which correspondingly increased the z-average due to agglomeration. Curcumin release from CS-NPs was slowest at chitosan to TPP weight ratio of 3:1, with a significant retention (36%) at the end of 6 h. Adsorption isotherms of mucin on CS-NPs fitted both the Freundlich and Langmuir models, suggesting a monolayer-limited adsorption on heterogeneous sites with varied affinities. Encapsulated curcumin exerted an influence on the adsorption of mucin due to H-bonding as well as π-π interactions between the phenolic moieties of curcumin and mucin.
Nanocrystalline SnO(x) (x = 1-2) thin films were prepared on glass substrates by a simple chemical bath deposition method. Triethanolamine was used as complexing agent to decrease time and temperature of deposition and shift the pH of the solution to the noncorrosive region. The films were characterized for composition, surface morphology, structure and optical properties. X-ray diffraction analysis confirms that SnO(x) thin films consist of a polycrystalline structure with an average grain size of 36 nm. Atomic force microscopy studies show a uniform grain distribution without pinholes. The elemental composition was evaluated by energy dispersive X-ray spectroscopy. The average O/Sn atomic percentage ratio is 1.72. Band gap energy and optical transition were determined from optical absorbance data. The film was found to exhibit direct and indirect transitions in the visible spectrum with band gap values of about 3.9 and 3.7 eV, respectively. The optical transmittance in the visible region is 82%. The SnO(x) nanocrystals exhibit an ultraviolet emission band centered at 392 nm in the vicinity of the band edge, which is attributed to the well-known exciton transition in SnO(x). Photosensitivity was detected in the positive region under illumination with white light.
Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (P<0.01), 24h after treatment with 25μg/ml AgNPs. In contrast, following pre-incubation of AgNPs with Curosurf(®), this effect was almost completely abolished. We further determined that the mechanism of this toxicity is likely associated with Ag(+) ion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs.
Matched MeSH terms: Metal Nanoparticles/toxicity*; Metal Nanoparticles/ultrastructure
Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies. Among all the formulations prepared with different cross linkers, CS-TPP-siRNA had the smallest particle size (ranged from 127 ± 9.7 to 455 ± 12.9 nm) with zeta potential ranged from +25.1 ± 1.5 to +39.4 ± 0.5 mV, and high entrapment (>95%) and binding efficiencies. Similarly, CS-TPP nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-TPP-siRNA nanoparticles in contrast to irregular morphology displayed by CS-DS-siRNA and CS-PGA-siRNA nanoparticles. All siRNA loaded CS-TPP/DS/PGA nanoparticles showed initial burst release followed by sustained release of siRNA. Moreover, all the formulations showed low and concentration-dependent cytotoxicity with human colorectal cancer cells (DLD-1), in vitro. The cellular uptake studies with CS-TPP-siRNA nanoparticles showed successful delivery of siRNA within cytoplasm of DLD-1 cells. The results demonstrate that ionically cross-linked CS-TPP nanoparticles are biocompatible non-viral gene delivery system and generate a solid ground for further optimization studies, for example with regard to steric stabilization and targeting.
In the present study, we have developed a green approach for the synthesis of silver nanoparticles (DSAgNPs) using aqueous extract of Durio zibethinus seed and determined its antibacterial, photocatalytic and cytotoxic effects. Surface plasmon resonance confirmed the formation of DSAgNPs with a maximum absorbance (λmax) of 420 nm. SEM and TEM images revealed DSAgNPs were spherical and rod shaped, with a size range of 20 nm and 75 nm. The zeta potential was found to be -15.41 mV. XRD and EDX analyses confirmed the nature and presence of Ag and AgCl. DSAgNPs showed considerable antibacterial activity, exhibited better cytotoxicity against brine shrimp, and shown better photocatalytic activity against methylene blue. Based on the present research work, it can be concluded that DSAgNPs could be used in the field of water treatment, pharmaceuticals, biomedicine, biosensor and nanotechnology in near future.
Matched MeSH terms: Metal Nanoparticles/ultrastructure; Metal Nanoparticles/chemistry*
To examine the human exposure to a novel silver and copper nanoparticle (AgNP and CuNP)/polystyrene-polyethylene oxide block copolymer (PS-b-PEO) food packaging coating, the migration of Ag and Cu into 3% acetic acid (3% HAc) food simulant was assessed at 60 °C for 10 days. Significantly lower migration was observed for Ag (0.46 mg/kg food) compared to Cu (0.82 mg/kg food) measured by inductively coupled plasma - atomic emission spectrometry (ICP-AES). In addition, no distinct population of AgNPs or CuNPs were observed in 3% HAc by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The predicted human exposure to Ag and Cu was used to calculate a margin of exposure (MOE) for ionic species of Ag and Cu, which indicated the safe use of the food packaging in a hypothetical scenario (e.g. as fruit juice packaging). While migration exceeded regulatory limits, the calculated MOE suggests current migration limits may be conservative for specific nano-packaging applications.
Matched MeSH terms: Metal Nanoparticles/analysis*; Metal Nanoparticles/chemistry