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INVITED REVIEW
Year : 2010  |  Volume : 2  |  Issue : 4  |  Page : 282-289 Table of Contents     

Introduction to metallic nanoparticles


1 Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, 1060 Dragon Road, Oakwood, Virginia 246 14, USA
2 Department of Radiology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 753 90, USA
3 Department of Radiology, Dr. L.H. Hiranandani College of Pharmacy, Mumbai University, Ulhasnagar-421 003, India

Date of Submission21-Jun-2010
Date of Decision24-Jul-2010
Date of Acceptance28-Aug-2010
Date of Web Publication28-Oct-2010

Correspondence Address:
Vicky V Mody
Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, 1060 Dragon Road, Oakwood, Virginia 246 14
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0975-7406.72127

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   Abstract 

Metallic nanoparticles have fascinated scientist for over a century and are now heavily utilized in biomedical sciences and engineering. They are a focus of interest because of their huge potential in nanotechnology. Today these materials can be synthesized and modified with various chemical functional groups which allow them to be conjugated with antibodies, ligands, and drugs of interest and thus opening a wide range of potential applications in biotechnology, magnetic separation, and preconcentration of target analytes, targeted drug delivery, and vehicles for gene and drug delivery and more importantly diagnostic imaging. Moreover, various imaging modalities have been developed over the period of time such as MRI, CT, PET, ultrasound, SERS, and optical imaging as an aid to image various disease states. These imaging modalities differ in both techniques and instrumentation and more importantly require a contrast agent with unique physiochemical properties. This led to the invention of various nanoparticulated contrast agent such as magnetic nanoparticles (Fe 3 O 4 ), gold, and silver nanoparticles for their application in these imaging modalities. In addition, to use various imaging techniques in tandem newer multifunctional nanoshells and nanocages have been developed. Thus in this review article, we aim to provide an introduction to magnetic nanoparticles (Fe 3 O 4 ), gold nanoparticles, nanoshells and nanocages, and silver nanoparticles followed by their synthesis, physiochemical properties, and citing some recent applications in the diagnostic imaging and therapy of cancer.

Keywords: Fe 3 O 4 , gold nanoparticles, iron oxide nanoparticles, metallic nanoparticles, nanocages, nanoshells, silver nanoparticles


How to cite this article:
Mody VV, Siwale R, Singh A, Mody HR. Introduction to metallic nanoparticles. J Pharm Bioall Sci 2010;2:282-9

How to cite this URL:
Mody VV, Siwale R, Singh A, Mody HR. Introduction to metallic nanoparticles. J Pharm Bioall Sci [serial online] 2010 [cited 2021 Dec 6];2:282-9. Available from: https://www.jpbsonline.org/text.asp?2010/2/4/282/72127

Nanotechnology refers to the branch of science and engineering dedicated to materials, having dimensions in the order of 100th of nm or less. [1] The term being new, but has been widely used for the development of more efficient technology. In recent years, nanotechnology has been embraced by industrial sectors due to its applications in the field of electronic storage systems, [2] biotechnology, [3] magnetic separation and preconcentration of target analytes, targeted drug delivery, [4],[5] and vehicles for gene and drug delivery. [2],[4],[5],[6] Consequently, with wide range of applications available, these particles have potential to make a significant impact to the society. Although new, the history of nanomaterials dates long back to 1959, when Richard P. Feynman, a physicist at Cal Tech, forecasted the advent of nanomaterials. In one of his class he said, "There is plenty of room at the bottom," and suggested that scaling down to nanolevel and starting from the bottom was the key to future technology and advancement. [6] As the field of nanotechnology advanced, novel nanomaterials become apparent having different properties as compared to their larger counterparts. This difference in the physiochemical properties of nanomaterials can be attributed to their high surface-to-volume ratio. Due to these unique properties, they make excellent candidate for biomedical applications as variety of biological processes occur at nanometer scales.

In general, nanoparticles used in the field of biotechnology range in particle size between 10 and 500 nm, seldom exceeding 700 nm. The nanosize of these particles allows various communications with biomolecules on the cell surfaces and within the cells in way that can be decoded and designated to various biochemical and physiochemical properties of these cells. [7] Similarly, its potential application in drug delivery system and noninvasive imaging offered various advantages over conventional pharmaceutical agents. [7] In an effort to utilize nanoparticles at their full throttle, it is important that the nanoparticulate systems should be stable, biocompatible, and selectively directed to specific sites in the body after systemic administration. More specific targeting systems are designed to recognize the targeted cells such as cancer cells. This can be achieved by conjugating the nanoparticle with an appropriate ligand, which has a specific binding activity with respect to the target cells. In addition, nanoparticles provide a platform to attach multiple copies of therapeutic substance on it and hence increase the concentration of therapeutic and diagnostic substances at the pathological site. Also, the concentration and dynamics of the active molecule can be varied by controlling the particle size of nanoparticles (>3-5 nm). This control in particle size in conjugation with surface coating with stealth ligand allows them to veil against body's immune system, enabling them to circulate in the blood for longer period of time. [7] These advances in the field of biotechnology have opened an endless opportunities for molecular diagnostics and therapy. [8] Once targeted (active or passive), these nanocarriers can be designed in a way to facilitate them to act as imaging probes using variety to techniques such as ultrasound (US), X-ray, computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), optical imaging, and surface-enhanced Raman imaging (SERS) [Table 1]. [9] Hence, these so-called "molecular imaging probes" can noninvasively provide valuable information about differentiate abnormalities in various body structures and organs to determine the extent of disease, and evaluate the effectiveness of treatment. [7] Thus short molecular imaging enables the visualization of the cellular function and the follow-up of the molecular process in living organisms without perturbing them. [10]
Table 1 :Comparison of common imaging techniques along with the nanoparticles currently used or under clinical trials[10]

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Over the year's nanoparticles such as magnetic nanoparticles (iron oxide), gold and silver nanoparticles, nanoshells, and nanocages have been continuously used and modified to enable their use as a diagnostic and therapeutic agent. Thus, in this particular review article we have introduced iron oxide, gold, and silver nanoparticles along with newer nanoshells and nanocages. These are then briefly discussed for their method of development and some citing recent examples which utilize their intrinsic properties as diagnostic and/or therapeutic agents for diseases, mainly cancer.


   Iron Oxide Nanoparticles Top


Iron (III) oxide (Fe 2 O 3 ) is a reddish brown, inorganic compound which is paramagnetic in nature and also one of the three main oxides of iron, while other two being FeO and Fe 3 O 4 . The Fe 3 O 4 , which also occurs naturally as the mineral magnetite, is also superparamagnetic in nature. Due to their ultrafine size, magnetic properties, and biocompatibility, superparamagnetic iron oxide nanoparticles (SPION) have emerged as promising candidates for various biomedical applications, such as enhanced resolution contrast agents for MRI, targeted drug delivery and imaging, hyperthermia, gene therapy, stem cell tracking, molecular/cellular tracking, magnetic separation technologies (e.g., rapid DNA sequencing) early detection of inflammatory, cancer, diabetes, and atherosclerosis. [11],[12],[13],[14],[15],[16],[17],[18],[19],[20] All these biomedical applications require that the nanoparticles have high magnetization values so as to provide high-resolution MR images. In general, the superparamagnetic nanoparticles resemble excellent imaging probes to be used as MRI contrast agents since the MR signal intensity is significantly modulated without any compromise in its in vivo stability. [21] Basically, all contrast agents induce a decrease in the T1 and T2 relaxation times of surrounding water protons and thereby manipulate the signal intensity of the imaged tissue. [22]

Converging advances in the understanding of the molecular biology of various diseases recommended the need of homogeneous and targeted imaging probes along with a narrow size distribution in between 10 and 250 nm in diameter. Developing magnetic nanoparticles in this diameter range is a complex process and various chemical routes for their synthesis have been proposed. These methods include microemulsions, sol−gel syntheses, sonochemical reactions, hydrothermal reactions, hydrolysis and thermolysis of precursors, flow injection syntheses, and electrospray syntheses. [23],[24],[25],[26],[27],[28],[29] However, the most common method for the production of magnetite nanoparticles is the chemical coprecipitation technique of iron salts. [30],[31],[32],[33],[34] The main advantage of the coprecipitation process is that a large amount of nanoparticles can be synthesized but with limited control on size distribution. This is mainly due to that the kinetic factors are controlling the growth of the crystal. Thus the particulate magnetic contrast agents synthesized using these methods include ultrasmall particles of iron oxide (USPIO) (10-40 nm), small particles of iron oxide (SPIO) (60-150 nm). Besides, monocrystalline USPIOs are also called as monocrystalline iron oxide nanoparticles (MIONs), whereas MIONs when cross-linked with dextran they are called crosslinked iron oxide nanoparticles CLIO (10-30 nm). [35],[36],[37] The modification of the dextran coating by carboxylation leads to a shorter clearance half-life in blood. [38] Hence, ferumoxytol (AMAG Pharmaceuticals), a carboxyalkylated polysaccharide coated iron oxide nanoparticle, is already described as a good first-pass contrast agent but uptake by macrophages is unspecific and too fast to enhance the uptake in macrophage-rich plaques.

In order to improve the cellular uptake, these particles can be modified with a peculiar surface coating so that they can be easily conjugated to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumor [Figure 1]. [7],[39] While traditional contrast agents distribute rather nonspecifically, targeted molecular imaging probes based on iron oxide nanoparticles have been developed that specifically target body tissue or cells. [7],[40] For instance, Conroy and coworkers developed (chlorotoxin (CTX)) a biocompatible iron oxide nanoprobe coated with poly(ethylene glycol) (PEG), which is capable of specifically targeting glioma tumors via the surface-bound targeting peptide. [41] Further, MRI studies showed the preferential accumulation of the nanoprobe within gliomas. In another study, Apopa et al. engineered iron oxide nanoparticles that can induce an increase in cell permeability through the production of reactive oxygen species (ROS) and the stabilization of microtubules. [42] These are the few applications of iron oxide nanoparticles in biomedical imaging.
Figure 1 :Schematic diagram representing the fucntionalization of magnetic nanoparticles with bioresponsive peptide, PEG linker, chemotherapeutic agent, antibody, and cell-penetrating peptide.[11]

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These studies provide a new insight into the bioreactivity of engineered iron nanoparticles, which can provide potential applications in medical imaging or drug delivery. The further development and modification of the complexes of iron oxide along with dendrimers, polymeric nanoparticles, liposomes, and solid lipid nanoparticles are widely studied. However, the toxicity of these magnetic nanoparticles to certain types of neuronal cells is still the matter of concern. [43]


   Gold Nanoparticles Top


Colloidal gold, also known as gold nanoparticles, is a suspension (or colloid) of nanometer-sized particles of gold. The history of these colloidal solutions dates back to Roman times when they were used to stain glass for decorative purposes. [44] However, the modern scientific evaluation of colloidal gold did not begin until Michael Faraday's work of the 1850s, when he observed that the colloidal gold solutions have properties that differ from the bulk gold. [45],[46] Hence the colloidal solution is either an intense red color (for particles less than 100 nm) or a dirty yellowish color (for larger particles) as shown in [Figure 2] and [Figure 3]. [47],[48] These interesting optical properties of these gold nanoparticles are due to their unique interaction with light. [49] In the presence of the oscillating electromagnetic field of the light, the free electrons of the metal nanoparticles undergo an oscillation with respect to the metal lattice. [50],[51],[52],[53] This process is resonant at a particular frequency of the light and is termed the localized surface plasmon resonance (LSPR). After absorption, the surface plasmon decays radiatively resulting in light scattering or nonradiatively by converting the absorbed light into heat. Thus for gold nanospheres with particle size around 10 nm in diameter have a strong absorption maximum around 520 nm in aqueous solution due to their LSPR. These nanoshperes show a stokes shift with an increase in the nanosphere size due to the electromagnetic retardation in larger particles.
Figure 2 :Photographs of aqueous solutions of gold nanospheres (upper panels) and gold nanorods (lower panels) as a function of increasing dimensions. Corresponding transmission electron microscopy images of the nanoparticles are shown (all scale bars 100 nm). The difference in color of the particle solutions is more dramatic for rods than for spheres. This is due to the nature of plasmon bands (one for spheres and two for rods) that are more sensitive to size for rods compared with spheres. For spheres, the size varies from 4 to 40 nm (TEMs a-e), whereas for rods, the aspect ratio varies from 1.3 to 5 for short rods (TEMs f-j) and 20 (TEM k) for long rods[50]

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Figure 3 :Gold nanorods (NRs) with tunable optical absorptions at visible and near-infrared wavelengths; a) Optical absorption spectra of gold NRs with different aspect ratios (a-e); b) Color wheel, with reference to gold NRs labeled a-e. TR, transverse resonance[51]

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Moreover, the properties and applications of colloidal gold nanoparticles also depend upon its shape. [Figure 2] shows that the difference in color of the particle solutions is more dramatic for rods than for spheres. For example, the rod-shaped nanoparticles have two resonances: one due to plasmon oscillation along the nanorod short axis and another due to plasmon oscillation along the long axis, which depends strongly on the nanorod aspect ratio, that is, length-to-width ratio. [54],[55] When the nanorod aspect ratio is increased, the long-axis LSPR wavelength position red shifts from the visible to the NIR and also progressively increases in oscillator strength [Figure 2]. [55] For example, rodlike particles have both transverse and longitudinal absorption peak, and anisotropy of the shape affects their self-assembly. [56] Due to these unique optical properties, gold nanoparticles are the subject of substantial research, with enormous applications including biological imaging, electronics, and materials science. [57] Thus to develop gold nanoparticles for specific applications, reliable and high-yielding methods including those with spherical and nonspherical shapes have been developed over the period of years. [56],[58]

The most prevalent method for the synthesis of monodisperse spherical gold nanoparticles was pioneered by Turkevich et al. in 1951 and later refined by Frens et al. in 1973. [59],[60],[61],[62] This method uses the chemical reduction of gold salts such as hydrogen tetrachloroaurate (HAuCl 4 ) using citrate as the reducing agent. This method produces monodisperse spherical gold nanoparticles in the range of 10-20 nm in diameter. However, the synthesis of larger gold nanoparticles with diameters between 30 and 100 nm was reported by Brown and Natan via seeding of Au 3+ by hydroxylamine. [63] Subsequent research led to the modification of the shape of these gold nanoparticles resulting in rod, triangular, polygonal rods, and spherical particles. [64],[65],[66] These ensuing gold nanoparticles have unique properties, providing a high surface area to volume ratio. Moreover, the gold surface offers a unique opportunity to conjugate ligands such as oligonucleotides, proteins, and antibodies containing functional groups such as thiols, mercaptans, phosphines, and amines, which demonstrates a strong affinity for gold surface. [67] The realization of such gold nanoconjugates coupled with strongly enhanced LSPR gold nanoparticles have found applications in simpler but much powerful imaging techniques such as dark-field imaging, SERS, and optical imaging for the diagnosis of various disease states. [68]

In fact, El Sayed et al. have established the use of gold nanoparticles for cancer imaging by selectively transporting AuNPs into the cancer cell nucleus. In order to selectively transport the AuNPs into the cancer cell nucleus, they conjugated arginine−glycine−aspartic acid peptide (RGD) and a nuclear localization signal peptide (NLS) to a 30-nm AuNPs via PEG. [69] RGD is known to target αvβ6 integrins receptors on the surface of the cell, whereas NLS sequence lysine−lysine−lysine−arginine−lysine (KKKRK) sequence is known to associate with karyopherins (importins) in the cytoplasm, which enables the translocation to the nucleus. [70],[71],[72] Thus the presence of RGD will enable cancer-cell-specific targeting, whereas the presence of NLS will exhibit cancer cell nucleus specific targeting. This intuitively developed particle was then targeted to human oral squamous cell carcinoma (HSC) having αvβ6 integrins overexpressed on the cell surface (cancer model), and human keratinocytes (HaCat) (control). The authors further demonstrated that RGD-AuNPs specifically target the cytoplasm of cancer cells [Figure 4]a over that of normal cells [Figure 4]c, and the RGD/NLS-AuNPs specifically target the nuclei of cancer cells [Figure 4]b over those of normal cells [Figure 4]d. [69]
Figure 4 :Dark field light scattering images of cytoplasm and nuclear targeting AuNPs. a) RGD-AuNPs located in the cytoplasm of cancer cells. b) RGD/NLS-AuNPs located at the nucleus of cancer cells. c) RGD-AuNPs located in the cytoplasm of normal cells. d) RGD/NLS-AuNPs located at the nucleus of normal cells. The cancer and normal cells were incubated in the presence of these AuNPs at a concentration of 0.4 nM for 24 hours and these images clearly display the efficient uptake of AuNPs in cancer cells compared with normal cells. Scale bar 10 μm[72]

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Similarly, Qian et al. reported the development of tumor-targeted gold nanoparticles as a probe for Raman scatters in vivo. [73] These gold nanoparticles were encoded with a Raman reporter and further encapsulated with a thiol-modified PEG coat. Additionally, to specifically target tumor cells, the pegylated gold nanoparticles were then conjugated with an antibody against epidermal growth factor receptor, which is sometimes overexpressed in certain types of cancer cells. The Raman enhancement from these tailored particles was then observed with electronic transitions at 633 or 785 nm via SERS. The results obtained by Qian and coworkers suggest the highly specific recognition and detection of human cancer cells, as well as active targeting of EGFR-positive tumor xenografts in animal models can be made using SERS. [73]

Moreover, the use of gold nanorods as photothermal agents sets them apart from all nanoprobes. Photothermal therapy (PTT) is a procedure in which a photosensitizer is excited with specific band light (mainly IR). This activation brings the sensitizer to an excited state where it then releases vibrational energy in the form of heat. The heat is the actual method of therapy that kills the targeted cells. One of the biggest recent successes in photothermal therapy is the use of gold nanoparticles. Spherical gold nanoparticles absorptions have not been optimal for in vivo applications. This is because the peak absorptions have been limited to 520 nm for 10 nm diameter. Moreover, skin, tissues, and hemoglobin have a transmission window from 650 up to 900 nm. This was circumvented by the recent invention of gold nanorods by Murphy and Coworkers, who were able to tune the absorption peak of these nanoparticles, which can also be tuned from 550 nm up to 1 ΅m just by altering its aspect ratio of the nanorods [Figure 3]. [48],[74] Hence, for the rod-shaped gold nanoparticles with the absorption in the IR region, when selectively accumulated in tumors when bathed in laser light (in the IR region), the surrounding tissue is barely warmed, but the nanorods convert light to heat, killing the malignant cells. This potential application of gold nanorods sanctifies them from other nanoprobes. However, their incompatibility with other high-resolution imaging techniques such as MRI and irreproducibility in shapes led to the invention of nanocages and nanoshells.


   Nanoshells and Nanocages Top


Neeves and Birnboim calculated that a composite spherical particle consisting of a metallic shell and a dielectric core could give rise to LSPR modes with their wavelengths tunable over a broad range of the electromagnetic spectrum. [75] Later on, the experimental and theoretical work by Naomi Halas and Peter Nordlander at Rice University showed that the resonance of a silica-gold nanoshell particle can easily be positioned in the near-infrared (800-1,300 nm) region, where absorption by biomatters is low [Figure 5]. [76],[77],[78] They developed silica-gold nanospheres by using freshly formed amine-terminated silica spheres. These amine terminated silica spheres were then treated with a suspension of gold colloids (1-2 nm in size). Gold was deposited via chemical reduction to cover the silica core and to the amine terminal of the silicon core. Although this method is widely used, the intricacy involved in the control of thickness and smoothness of the metallic shells makes this method unsuitable for the routine synthesis of controlled particle-sized nanoshells. Furthermore, they also showed the successful irreversible photothermal ablation of tumor tissue both in vitro and in vivo when these nanoshells were localized onto the tumor cells. In another study, Halas and West established the use of near-infrared resonant nanoshells for whole-blood immunoassays. They further showed that the nanoshells when conjugated with antibodies act as recognition sites for a specific analyte [Figure 6]. The analyte causes the formation of dimmers, which will modify the LSPR. [79] Subsequent work in this field led to the development of the multifunctional magnetic gold nanoshells (Mag-GNS) by Jaeyun et al. utilizing Fe 3 O 4 nanoparticles as the magnetic core. The Fe 3 O 4 nanoparticles allow MRI for diagnosis, and the gold nanoshells enable photothermal therapy. By attaching an antibody to the Mag-GNS by a PEG linker, cancer cells can be targeted. Once localized, these particles enable the detection of cancer using MRI, whereas the photothermal therapy can be used to get rid of cancer cells. [80]
Figure 5 :G old nanoshell plasmon resonances for a 120-nm core with indicated shell thickness[81]

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Figure 6 :Formation of nanoshell dimer with the interaction of antibodies immobilized on the surface of the nanoshells[82]

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Similar to gold nanoshells, gold nanocages represent a novel class of nanostructures that are hollow porous gold nanoparticles that absorb light in the near-infrared range. They were first developed by the Xia and Coworkers via the reaction of silver nanoparticles with chloroauric acid (HAuCI 4 ) in boiling water. [81] Their LSPR peaks can also be tuned to the near infrared region by controlling the thickness and porosity of the walls. Comparable to nanoshells they have found applications in drug delivery and/or controlled drug release. Furthermore, the hollow interiors can host small objects such as magnetic nanoparticles to construct multifunctional hybrid nanostructures diagnostic imaging and therapy.


   Silver Nanoparticles Top


Silver nanoparticles are the particles of silver, with particle size between 1 and 100 nm in size. While frequently described as being "silver" some are composed of a large percentage of silver oxide due to their large ratio of surface to bulk silver atoms. Like gold nanoparticles, ionic silver has a long history and was initially used to stain the glass for yellow. Currently, there is also an effort to incorporate silver nanoparticles into a wide range of medical devices, including bone cement, surgical instruments, surgical masks, etc. Moreover, it has also been shown that ionic silver, in the right quantities, is suitable in treating wounds. [82],[83],[84] In fact, silver nanoparticles are now replacing silver sulfadiazine as an effective agent in the treatment of wounds. Additionally, Samsung has created and marketed a material called Silver Nano, which includes silver nanoparticles on the surfaces of household appliances. Moreover, due to their attractive physiochemical properties these nanomaterials have received considerable attention in biomedical imaging using SERS. In fact, the surface plasmon resonance and large effective scattering cross-section of individual silver nanoparticles make them ideal candidates for molecular labeling. [85] Thus many targeted silver oxide nanoprobes are currently being developed.

Typically, they are synthesized by the reduction of a silver salt with a reducing agent like sodium borohydride in the presence of a colloidal stabilizer. The most common colloidal stabilizers used are polyvinyl alcohol, poly(vinylpyrrolidone), bovine serum albumin (BSA), citrate, and cellulose. Newer novel methods include the use of ί-d-glucose as a reducing sugar and a starch as the stabilizer to develop silver nanoparticles ion implantation used to create silver nanoparticles. [86] Also, it is important to note that not all nanoparticles created are equal. The size and shape have been shown to have an impact on its efficacy. In fact, Elechiguerra et al. demonstrated that silver nanoparticles undergo a size-dependent interaction with HIV-1, with particles exclusively in the range of 1-10 nm attached to the virus. [87] They further suggest that silver nanoparticles interact with the HIV-1 virus via preferential binding to the gp120 glycoprotein knobs. [87] Similarly, Furno and Coworkers have developed biomaterials by impregnating silicone coated with silver oxide nanoparticles using supercritical carbon dioxide. [88] These novel biomaterials were developed with an aim to reduce the antibacterial infection. The results obtained were mixed but the methodology allows for the first-time silver impregnation (as opposed to coating) of medical polymers and promises to lead to an antimicrobial biomaterial. [88]

Even though these particles are not as widely preferred as compared to the gold nanoparticles and nanoshells, but they have made a tremendous impact on today's era of medical science. The interesting property of the noble metals is a promise that they would be continuously used as newer applications and protocols are being developed.


   Conclusion Top


This review article provides a glimpse to some simpler nanoparticles which are being currently modified for their potential applications in medicine. However, the field of nanoscience has blossomed over the last two decades and the need for nanotechnology to explore beyond the cells walls has become more important. [89] Nanoparticles have successfully come to aid various disease states, but the advances in biomedical imaging depend largely on the shape, size, and selectivity of the nanoparticle to the target. [89] Moreover, the type of the particle synthesized also governs the imaging modality to be used and thus the cost of diagnosis. Even though current investigations have demonstrated that multivalent composite materials can provide significant advantages, the ambiguity in developing them for a particular target with high specificity is still challenging. Fortunately, the field of nanotechnology continues to grow interest within the chemical research community with major discoveries as well as new scientific challenges. [44] Nevertheless, the future studies should also aim to address safety and biocompatibility of these nanoparticles, in particular long-term toxicities. [90] Additional clinical studies on humans and on animal models should be performed to substantiate their use especially in biomedical imaging using MRI, CT, ultrasound, PET, SERS, and optical imaging. [90]

 
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48 Novel Eco-Friendly Synthesis of Biosilver Nanoparticles as a Colorimetric Probe for Highly Selective Detection of Fe (III) Ions in Aqueous Solution
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54 Recapitulation of Cancer Nanotherapeutics
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56 Nanotechnology and Animal Health
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58 Near-infrared Light and Metallic Nanoparticles
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59 Mechanisms of Macrophage Plasticity in the Tumor Environment: Manipulating Activation State to Improve Outcomes
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60 Emerging Concern for Silver Nanoparticle Resistance in Acinetobacter baumannii and Other Bacteria
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61 External and Internal Stimuli-Responsive Metallic Nanotherapeutics for Enhanced Anticancer Therapy
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62 Nanoantibiotics: Functions and Properties at the Nanoscale to Combat Antibiotic Resistance
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63 Discovery, Optimization, and Clinical Application of Natural Antimicrobial Peptides
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64 Do Lipid-based Nanoparticles Hold Promise for Advancing the Clinical Translation of Anticancer Alkaloids?
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65 Electroactive Polymeric Composites to Mimic the Electromechanical Properties of Myocardium in Cardiac Tissue Repair
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66 Nanocarrier-Mediated Topical Insulin Delivery for Wound Healing
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67 Effect of Saffron Extract on the Hepatotoxicity Induced by Copper Nanoparticles in Male Mice
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68 The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update
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70 Plasmonic Nanoparticles as Optical Sensing Probes for the Detection of Alzheimer’s Disease
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72 Toward a Better Understanding of Metal Nanoparticles, a Novel Strategy from Eucalyptus Plants
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73 SCREENING OF BIODEGRADABLE POLYMER AND MOST EFFECTIVE VARIABLES IN PREPARATION OF ESSENTIAL OIL LOADED NANO PARTICLES FOR PULMONARY DELIVERY USING TAGUCHI DESIGN
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74 Green Synthesis of Fe2O3 Nanoparticles from Orange Peel Extract and a Study of Its Antibacterial Activity
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75 Optimized Polyethylene Glycolylated Polymer–Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment
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76 Current Research of Graphene-Based Nanocomposites and Their Application for Supercapacitors
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77 Green Synthesis of Silver Nanoparticles Using Astragalus tribuloides Delile. Root Extract: Characterization, Antioxidant, Antibacterial, and Anti-Inflammatory Activities
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79 Antifungal and Cytotoxic Evaluation of Photochemically Synthesized Heparin-Coated Gold and Silver Nanoparticles
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80 Advances in Ultrasonic Spray Pyrolysis Processing of Noble Metal Nanoparticles—Review
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81 Creating Structured Hydrogel Microenvironments for Regulating Stem Cell Differentiation
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82 Nanoapproaches to Modifying Epigenetics of Epithelial Mesenchymal Transition for Treatment of Pulmonary Fibrosis
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83 Nanoparticles as Potential Antivirals in Agriculture
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85 Nanodelivery of Natural Antioxidants: An Anti-aging Perspective
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86 Injectable Hydrogel-Based Nanocomposites for Cardiovascular Diseases
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87 An Overview of Strategic Non-Biological Approaches for The Synthesis of Cupper Nanoparticles
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88 The Use of Montmorillonite (MMT) in Food Nanocomposites: Methods of Incorporation, Characterization of MMT/Polymer Nanocomposites and Main Consequences in the Properties
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89 Nanocarriers(s) Based Approaches in Cancer Therapeutics
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90 Metalik nanopartiküllerin hedeflendirilmesi
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91 Atherosclerosis and Nanomedicine Potential: Current Advances and Future Opportunities
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92 Trends in Nanomedicines for Cancer Treatment
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93 Nanobulges: A Duplex Nanosystem for Multidimensional Applications
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94 Nanomaterial integration into the scaffolding materials for nerve tissue engineering: a review
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95 The Effects of Polymer Coating of Gold Nanoparticles on Oxidative Stress and DNA Damage
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96 Microbial contamination and plaque scores of nanogold-coated toothbrush
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97 Synthesis of colloidal silver nanoparticles and their bactericidal effects on E. coli, S. epidermidis and oral plaque
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98 Characterization and antibacterial of Gold Nanoparticles Prepared by Electrolysis method
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99 Biosynthesis, antimicrobial spectra and applications of silver nanoparticles: current progress and future prospects
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100 Structural and optical studies of silver sulfide nanoparticles from silver(I) dithiocarbamate complex: molecular structure of ethylphenyl dithiocarbamato silver(I)
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101 Nanotheranostic agents for neurodegenerative diseases
Terry Tetley, Jorge Bernardino de la Serna, Sonia Antoranz Contera, Parasuraman Padmanabhan, Mathangi Palanivel, Ajay Kumar, Domokos Máthé, George K. Radda, Kah-Leong Lim, Balázs Gulyás
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102 Porous organic polymer material supported palladium nanoparticles
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103 Nanotechnology-based drug delivery systems for enhanced diagnosis and therapy of oral cancer
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104 Metal-Based Nanostructures/PLGA Nanocomposites: Antimicrobial Activity, Cytotoxicity, and Their Biomedical Applications
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105 Integrated analytical platforms for the comprehensive characterization of bioconjugated inorganic nanomaterials aiming at biological applications
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106 Highly stable AgNPs prepared via a novel green approach for catalytic and photocatalytic removal of biological and non-biological pollutants
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109 Big impact of nanoparticles: analysis of the most cited nanopharmaceuticals and nanonutraceuticals research
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112 Synthesis, characterization and biocompatibility studies of carbon quantum dots from Phoenix dactylifera
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113 Recent advances in understanding oligonucleotide aptamers and their applications as therapeutic agents
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114 Structural, Morphological and Biological Features of ZnO Nanoparticles Using Hyphaene thebaica (L.) Mart. Fruits
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115 Influence of PVP polymer concentration on nonlinear absorption in silver nanoparticles at resonant excitation
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116 First principle study of silver nanoparticle interactions with antimalarial drugs extracted from Artemisia annua plant
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117 Nanodelivery of phytobioactive compounds for treating aging-associated disorders
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118 Synthesis of Metal Nanostructures Using Supercritical Carbon Dioxide: A Green and Upscalable Process
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119 Potential Applications of Advanced Nano/Hydrogels in Biomedicine: Static, Dynamic, Multi-Stage, and Bioinspired
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120 Antimicrobial Metal Nanomaterials: From Passive to Stimuli-Activated Applications
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121 Label-free Immunosensor for the Determination of Microcystin-LR in Water
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122 Electrochemical Determination of Caffeine Using Bimetallic Au-Ag Nanoparticles Obtained from Low-cost Green Synthesis
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123 Properties of a-Brass Nanoparticles. 1. Neural Network Potential Energy Surface
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125 Water safety screening via multiplex LAMP-Au-nanoprobe integrated approach
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126 Citrate-silver nanoparticles and their impact on some environmental beneficial fungi
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128 Nanocarriers for effective nutraceutical delivery to the brain
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129 Ropinirole silver nanocomposite attenuates neurodegeneration in the transgenic Drosophila melanogaster model of Parkinson's disease
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135 Selection of resistance by antimicrobial coatings in the healthcare setting
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136 Enhancement the electrical conductivity of the synthesized polyvinylidene fluoride/polyvinyl chloride composite doped with palladium nanoparticles via laser ablation
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137 Effect of Phosphate, Sulfate, Arsenate, and Pyrite on Surface Transformations and Chemical Retention of Gold Nanoparticles (Au–NPs) in Partially Saturated Soil Columns
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139 Effect of Substrates on Catalytic Activity of Biogenic Palladium Nanoparticles in C–C Cross-Coupling Reactions
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140 Anticancer activity of green synthesised gold nanoparticles from Marsdenia tenacissima inhibits A549 cell proliferation through the apoptotic pathway
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141 Glycan Carriers As Glycotools for Medicinal Chemistry Applications
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142 Greener synthesis of ZnO and Ag–ZnO nanoparticles using Silybum marianum for diverse biomedical applications
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143 Prodrugs in combination with nanocarriers as a strategy for promoting antitumoral efficiency
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144 Microfluidically Assisted Construction of Hierarchical Multicomponent Microparticles for Short Intermediate Diffusion Paths in Heterogeneous Catalysis
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145 Enhanced anticancer effect of copper-loaded chitosan nanoparticles against osteosarcoma
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146 Effects of pulsed laser irradiation on gold-coated silver nanoplates and their antibacterial activity
Kaung Kyaw,Hiroaki Ichimaru,Takayuki Kawagoe,Mitsuhiro Terakawa,Yuta Miyazawa,Daigou Mizoguchi,Masayuki Tsushida,Takuro Niidome
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147 Nanoparticle-Based Immunochemical Biosensors and Assays: Recent Advances and Challenges
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148 Amplification of resonance Rayleigh scattering of gold nanoparticles by tweaking into nanowires: Bio-sensing of a-tocopherol by enhanced resonance Rayleigh scattering of curcumin capped gold nanowires through non-covalent interaction
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149 Nanoparticle-mediated drug delivery system for atherosclerotic cardiovascular disease
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150 Nano-therapeutics: A revolution in infection control in post antibiotic era
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151 Fabrication of adenosine 5'-triphosphate-capped silver nanoparticles: Enhanced cytotoxicity efficacy and targeting effect against tumor cells
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152 Biogenic synthesis of Marsilea quadrifolia gold nanoparticles: a study of improved glucose utilization efficiency on 3T3-L1 adipocytes
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153 Iron and iron oxide nanoparticles are highly toxic to Culex quinquefasciatus with little non-target effects on larvivorous fishes
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154 Laser-assisted fabrication and size distribution modification of colloidal gold nanostructures by nanosecond laser ablation in different liquids
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155 Implementation of nanoparticles in therapeutic radiation oncology
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156 Actinomycetes mediated synthesis of gold nanoparticles from the culture supernatant of Streptomyces griseoruber with special reference to catalytic activity
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157 Anthelmintic effects of zinc oxide and iron oxide nanoparticles against Toxocara vitulorum
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158 Green synthesis of silver nanoparticles using Azadirachta indica leaf extract and its antimicrobial study
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159 NANOTECHNOLOGY AS A POTENTIAL THERAPEUTIC ALTERNATIVE FOR SCHISTOSOMIASIS
Fernanda Tomiotto-Pellissier,Milena Menegazzo Miranda-Sapla,Laís Fernanda Machado,Bruna Taciane da Silva Bortoleti,Claudia Stoeglehner Sahd,Alan Ferreira Chagas,Joăo Paulo Assolini,Francisco José de Abreu Oliveira,Wander Rogério Pavanelli,Ivete Conchon-Costa,Idessania Nazareth Costa,Francine Nesello Melanda
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160 Recent progress in theranostic applications of hybrid gold nanoparticles
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161 Purification of Nanoparticles by Liquid Chromatography for Biomedical and Engineering Applications
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162 Heterogeneous Vascular Bed Responses to Pulmonary Titanium Dioxide Nanoparticle Exposure
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163 Metal-Based Nanoparticles for the Treatment of Infectious Diseases
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164 Antibacterial Activities of Silver Nanoplates Controlled by Pulsed Laser
Hiroaki ICHIMARU, Kaung KYAW, Takayuki KAWAGOE, Mitsuhiro TERAKAWA, Yuta MIYAZAWA, Daigou MIZOGUCHI, Masayuki TSUSHIDA, Takuro NIIDOME
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165 Therapeutic targeting in nanomedicine: the future lies in recombinant antibodies
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166 Green synthesis, characterisation and bioactivity of plant-mediated silver nanoparticles using Decalepis hamiltonii root extract
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167 Novel nanoparticulate systems for lung cancer therapy: an updated review
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168 Anticancer activity of metal nanoparticles and their peptide conjugates against human colon adenorectal carcinoma cells
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Artificial Cells, Nanomedicine, and Biotechnology. 2017; : 1
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169 Lyotropic liquid crystal-assisted synthesis of micro- and nanoparticles of silver
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Liquid Crystals. 2017; : 1
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170 Marine microorganisms as potential biofactories for synthesis of metallic nanoparticles
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171 Green Synthesis of Silver Nanoparticles: A Review
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Green and Sustainable Chemistry. 2016; 06(01): 34
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172 Green Synthesis of Smart Metal/Polymer Nanocomposite Particles and Their Tuneable Catalytic Activities
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173 Nanostructured materials functionalized with metal complexes: In search of alternatives for administering anticancer metallodrugs
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174 Biological activities of silver nanoparticles from Nothapodytes nimmoniana (Graham) Mabb. Fruit extracts.
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175 Synthesis and study of the catalytic applications in C–C coupling reactions of hybrid nanosystems based on alumina and palladium nanoparticles
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176 Oxidative stress in rat brain but not in liver following oral administration of a low dose of nanoparticulate silver
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177 Cancer nanotheranostics: Strategies, promises and impediments
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178 Metal Nanomaterial Toxicity Variations Within the Vascular System
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179 Eco-friendly decoration of graphene oxide with green synthesized silver nanoparticles: cytotoxic activity
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180 Cryo-electron microscopy and cryo-electron tomography of nanoparticles
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181 Synthesis of Monometallic Ru/TiO2 Catalysts and Selective Hydrogenation of CO2 to Formic Acid in Ionic Liquid
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182 Functional Improvement in Rats’ Pancreatic Islets Using Magnesium Oxide Nanoparticles Through Antiapoptotic and Antioxidant Pathways
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183 A biotechnological perspective on the application of iron oxide nanoparticles
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184 Biosynthesis of graphene-metal nanocomposites using plant extract and their biological activities
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185 Resonances of electromagnetic oscillations in a spherical metal nanoparticle
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186 Preparation and characterization of poly(ethylene glycol) stabilized nano silver particles by a mechanochemical assisted ball mill process
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187 Eco-friendly approach for nanoparticles synthesis and mechanism behind antibacterial activity of silver and anticancer activity of gold nanoparticles
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188 Cytotoxicity and genotoxicity of silver nanoparticles of different sizes in CHO-K1 and CHO-XRS5 cell lines
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189 Preparation, characterization and toxicological investigation of copper loaded chitosan nanoparticles in human embryonic kidney HEK-293 cells
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190 Enhanced photocatalytic and electrocatalytic applications of green synthesized silver nanoparticles
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191 Transport of engineered nanoparticles in partially saturated sand columns
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192 Phytosynthesized gold nanoparticles from C. roxburghii DC. leaf and their toxic effects on normal and cancer cell lines
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193 Facile synthesis of silver nanoparticles using Euphorbia antiquorum L. latex extract and evaluation of their biomedical perspectives as anticancer agents
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194 Biosynthesis of PVA encapsulated silver nanoparticles
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195 Current applications of nanoparticles in infectious diseases
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196 Triple Hit with Drug Carriers: pH- and Temperature-Responsive Theranostics for Multimodal Chemo- and Photothermal-Therapy and Diagnostic Applications
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197 Incorporation of gold nanoparticles into Langmuir-Blodgett films of polyaniline and montmorillonite for enhanced detection of metallic ions
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198 Manipulation of cluster formation through gas-wall boundary conditions in large area cluster sources
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199 Review of the Evidence from Epidemiology, Toxicology, and Lung Bioavailability on the Carcinogenicity of Inhaled Iron Oxide Particulates
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200 Soft-Nanocomposites of Nanoparticles and Nanocarbons with Supramolecular and Polymer Gels and Their Applications
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201 Integrated poly-d,l-lactide-co-glycolide/silver nanocomposite: synthesis, characterization and wound healing potential in Wistar Albino rats
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202 Synthesis and preliminary therapeutic evaluation of copper nanoparticles against diabetes mellitus and -induced micro- (renal) and macro-vascular (vascular endothelial and cardiovascular) abnormalities in rats
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203 Tuning surface accessibility and catalytic activity of Au nanoparticles through immobilization within porous-organic polymers
Rana R. Haikal,Ahmed M. Elmansi,Ahmed B. Soliman,Poussy Aly,Youssef S. Hassan,Mohamed R. Berber,Inas H. Hafez,Abdou Hassanien,Mohamed H. Alkordi
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204 Size-dependent cytotoxicity of copper oxide nanoparticles in lung epithelial cells
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205 On the formation of gold nanoparticles from [AuIIICl4]-and a non-classical reduced polyoxomolybdate as an electron source: a quantum mechanical modelling and experimental study
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206 Does surface coating of metallic nanoparticles modulate their interference with in vitro assays?
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207 On-column enzymatic synthesis of melanin nanoparticles using cryogenic poly(AAM-co-AGE) monolith and its free radical scavenging and electro-catalytic properties
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208 Optical paper-based sensor for ascorbic acid quantification using silver nanoparticles
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209 Nanoindentation in polymer nanocomposites
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210 Nanotheragnostic Applications for Ischemic and Hemorrhagic Strokes: Improved Delivery for a Better Prognosis
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211 Phytosynthesized iron nanoparticles: effects on fermentative hydrogen production by Enterobacter cloacae DH-89
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212 Current trends in medical image registration and fusion
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213 Noble metal nanoparticles embedding into polymeric materials: From fundamentals to applications
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214 Pseudomonas deceptionensisDC5-mediated synthesis of extracellular silver nanoparticles
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Artificial Cells, Nanomedicine, and Biotechnology. 2015; : 1
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215 In vitrotoxicological assessment of iron oxide, aluminium oxide and copper nanoparticles in prokaryotic and eukaryotic cell types
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216 Nanosensors for early cancer detection and for therapeutic drug monitoring
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217 Green sonochemical synthesis of silver nanoparticles at varying concentrations of ?-carrageenan
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218 A Review on Materials Derived from Polystyrene and Different Types of Nanoparticles
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219 Manufacturing nanomaterials: from research to industry
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220 Nanoparticles: synthesis and applications in life science and environmental technology
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221 Nanoapplications – From geckos to human health
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222 Nanoparticles in drug delivery: mechanism of action, formulation and clinical application towards reduction in drug-associated nephrotoxicity
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223 Nanoparticle-Mediated Drug Delivery System for Cardiovascular Disease
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224 Advanced human in vitro models to assess metal oxide nanoparticle-cell interactions
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225 Current methods for synthesis of gold nanoparticles
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226 Nano-Enhanced Adhesives
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227 Pharmacokinetics of metallic nanoparticles
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228 Antibacterial and cytotoxic potential of silver nanoparticles synthesized using latex of Calotropis gigantea L.
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229 A review with recent advancements on bioremediation-based abolition of heavy metals
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230 Effects of metal(loid)-based nanomaterials on essential element homeostasis: The central role of nanometallomics for nanotoxicology
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231 Dual application of Pd nanoparticles supported on mesoporous silica SBA-15 and MSU-2: supported catalysts for C–C coupling reactions and cytotoxic agents against human cancer cell lines
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232 Nitric Oxide Donors for Cardiovascular Implant Applications
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233 Nanoscale carriers for targeted delivery of drugs and therapeutic biomolecules
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234 Optimisation and enhancement of biohydrogen production using nickel nanoparticles – A novel approach
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235 Gold Nanoparticles and Nanocomposites in Clinical Diagnostics Using Electrochemical Methods
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236 In vitroeffect of gold and silver nanoparticles on human spermatozoa
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237 Surface enhanced fluorescence of anti-tumoral drug emodin adsorbed on silver nanoparticles and loaded on porous silicon
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