Nanomaterials that interact with light provide a unique opportunity for biophotonic nanomedicine. Multifunctional nanoparticles (NPs) that have strong and tunable surface plasmon resonance absorption in the near-infrared region combined with visibility with multiple imaging modalities (magnetic resonance imaging, nuclear imaging, and photoacoustic imaging) have great potential in image-guided therapies. These novel nanostructures, once introduced, are expected to home to solid tumors via the enhanced permeability and retention effect (a passive targeting mechanism) or via targeting ligands bound to their surfaces (an active targeting mechanism). The primary mode of action for photothermal conducting NPs is to convert photoenergy into heat, causing temperature in the treatment volume to be elevated above the thermal damage threshold, which results in irreversible cell killing. It is now recognized that this process, termed photothermal ablation therapy or PTA, although very effective, is unlikely to kill all tumor cells when used alone. In addition to PTA, photothermal conducting NPs can also efficiently trigger drug release and activate RNA interference. Such a multimodal approach, which permits simultaneous PTA therapy, chemotherapy, and therapeutic RNA interference, should provide an opportunity for complete eradication of residual disease.
In this Account, we provide an up-to-date review of the synthesis and characterization, functionalization, and in vitro and in vivo evaluation of NIR light-activatable multifunctional nanostructures used for imaging and therapy, with an emphasis on hollow gold nanospheres, magnetic core–shell gold nanoshells, and semiconductor copper monosulfide NPs. We discuss three types novel drug delivery systems in which hollow gold nanospheres are used to mediate controlled drug release.
Theranostics; hollow gold nanospheres; copper sulfide nanoparticles; near-infrared; drug delivery
Nano dense-silica (dSiO2) has many advantages such as adjustable core–shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.
Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core–shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core–shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW–SPION@dSiO2–YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW–SPION@dSiO2–YY146 to target tumor CD146.
800ZW–SPION@dSiO2–YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20–30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM−1·s−1. Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW–SPION@dSiO2–YY146 more than the control group 800ZW–SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW–SPION@dSiO2–YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.
This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW–SPION@dSiO2–YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery.
SPION; nanotechnology; EMT; SPION@dSiO2; xenograft; gastric cancer
Photothermal ablation based on resonant illumination of near-infrared-absorbing noble metal nanoparticles that have accumulated in tumors is a highly promising cancer therapy, currently in multiple clinical trials. A crucial aspect of this therapy is the nanoparticle size for optimal tumor uptake. A class of nanoparticles known as hollow Au (or Au–Ag) nanoshells (HGNS) is appealing because near-IR resonances are achievable in this system with diameters less than 100 nm. However, in this study, we report a surprising finding that in vivo HGNS are unstable, fragmenting with the Au and the remnants of the sacrificial Ag core accumulating differently in various organs. We synthesized 43, 62, and 82 nm diameter HGNS through a galvanic replacement reaction, with nanoparticles of all sizes showing virtually identical NIR resonances at ∼800 nm. A theoretical model indicated that alloying, residual Ag in the nanoparticle core, nanoparticle porosity, and surface defects all contribute to the presence of the plasmon resonance at the observed wavelength, with the major contributing factor being the residual Ag. While PEG functionalization resulted in stable nanoparticles under laser irradiation in solution, an anomalous, strongly element-specific biodistribution observed in tumor-bearing mice suggests that an avid fragmentation of all three sizes of nanoparticles occurred in vivo. Stability studies across a wide range of pH environments and in serum confirmed HGNS fragmentation. These results show that NIR resonant HGNS contain residual Ag, which does not stay contained within the HGNS in vivo. This demonstrates the importance of tracking both materials of a galvanic replacement nanoparticle in biodistribution studies and of performing thorough nanoparticle stability studies prior to any intended in vivo trial application.
plasmon; fragmentation; serum; near-infrared; photothermal therapy; nanomedicine; cancer
Recent advances in theranostics have expanded our ability to design and construct multifunctional nanoparticles that will ultimately allow us to image and treat diseases in a single clinical procedure. Theranostic nanoparticles, combining targeting, therapeutic and diagnostic functions within a single nanoscale complex, have emerged as a result of this confluence of nanoscience and biomedicine. The theranostic capabilities of gold nanoshells -spherical, silica core, gold shell nanoparticles- have attracted tremendous attention over the past decade as nanoshells have emerged as a promising tool for cancer therapy and bioimaging enhancement. This account examines the design and synthesis of nanoshell-based theranostic agents, their plasmon-derived optical properties and their corresponding applications. Nanoshells illuminated with resonant light are either strong optical absorbers or scatterers, properties which give rise to their unique capabilities. In this account, we discuss the underlying physical principles contributing to the photothermal response of nanoshells. We elucidate the photophysics of nanoshell-induced fluorescence enhancement of weak near-infrared fluorophores. We then describe the application of nanoshells as a contrast agent for optical coherence tomography of breast carcinoma cells in vivo. We also examine the recent progress of nanoshells as a multimodal theranostic probe for near-infrared fluorescence and magnetic resonance imaging (MRI) combined with photothermal ablation of cancer cells. The design and preparation of nanoshell complexes is discussed, and their ability to enhance the photoluminescence of fluorophores while incorporating MR contrast is described. We show the theranostic potential of the multimodal nanoshells in vivo for imaging subcutaneous breast cancer tumors in animal models and their biodistribution in various tissues.
We then discuss the potential of nanoshells as light-triggered gene therapy vectors. The plasmonic properties of nanoshells make them highly effective as light controlled delivery vectors, adding temporal control to the spatial control characteristic of nanoparticle-based gene therapy approaches. We describe the fabrication of DNA-conjugated nanoshell complexes and compare the efficiency of light-induced and thermally-induced DNA release of DNA. We examine light-triggered release of DAPI (4',6-diamidino-2-phenylindole) molecules, which bind reversibly to double-stranded DNA, to visualize intracellular light-induced release. Finally, we look at future prospects of nanoshell-based theranostics, the potential impact and near-term challenges of theranostic nanomedicine in the next decade.
Introducing hollow structures into metallic nanoparticles has become a promising route to improve their catalytic performances. A fundamental understanding of thermal stability of these novel nanostructures is of significance for their syntheses and applications. In this article, molecular dynamics simulations have been employed to offer insights into the thermodynamic evolution of hollow bimetallic core-shell nanoparticles. Our investigation reveals that for hollow Pt-core/Au-shell nanoparticle, premelting originates at the exterior surface, and a typical two-stage melting behavior is exhibited, similar to the solid ones. However, since the interior surface provides facilitation for the premelting initiating at the core, the two-stage melting is also observed in hollow Au-core/Pt-shell nanoparticle, remarkably different from the solid one. Furthermore, the collapse of hollow structure is accompanied with the overall melting of the hollow Pt-core/Au-shell nanoparticle while it occurs prior to that of the hollow Au-core/Pt-shell nanoparticle and leads to the formation of a liquid-core/solid-shell structure, although both of them finally transform into a mixing alloy with Au-dominated surface. Additionally, the existence of stacking faults in the hollow Pt-core/Au-shell nanoparticle distinctly lowers its melting point. This study could be of great importance to the design and development of novel nanocatalysts with both high activity and excellent stability.
We present a simplified synthesis of hollow gold nanoshells 20-50 nm in diameter via the well-established templated galvanic replacement reaction of silver for gold. The surface plasmon resonance absorbance of nanoshells made in this fashion can be tuned using basic colloid chemistry to control the size of the silver templates. The gold nanoshells can be varied in size and shell thickness depending on silver/gold reagent ratios and have an aqueous core. The template replacement chemistry is rapid, highly scalable, uses minimal amounts of toxic reagents, and in many cases is a true `one pot' synthesis. The smallest nanoshells (20 nm diameter, 7 nm wall thickness) reach the highest temperature on irradiation with femtosecond light pulses in the near infrared and anneal to form spherical nanoparticles fastest, even though their plasmon resonance does not overlap as well as the larger nanoshells (50 nm diameter, 7 nm wall thickness) with the 800 nm wavelength excitation. Optimizing a nanoshell structure to reach the highest nanoshell temperature is not the same as optimizing the structure for maximum energy absorbance.
Nanoparticles; galvanic replacement reactions; silver
Advances in nanostructure materials are leading to novel strategies for drug delivery and targeting, contrast media for magnetic resonance imaging (MRI), agents for hyperthermia and nanocarriers. Superparamagnetic iron oxide nanoparticles (SPIONs) are useful for all of these applications, and in drug-release systems, SPIONs allow for the localization, direction and concentration of drugs, providing a broad range of therapeutic applications. In this work, we developed and characterized polymeric nanoparticles based on poly (3-hydroxybutyric acid-co-hydroxyvaleric acid) (PHBV) functionalized with SPIONs and/or the antibiotic ceftiofur. These nanoparticles can be used in multiple biomedical applications, and the hybrid SPION–ceftiofur nanoparticles (PHBV/SPION/CEF) can serve as a multifunctional platform for the diagnosis and treatment of cancer and its associated bacterial infections.
Morphological examination using transmission electron microscopy (TEM) showed nanoparticles with a spherical shape and a core-shell structure. The particle size was evaluated using dynamic light scattering (DLS), which revealed a diameter of 243.0 ± 17 nm. The efficiency of encapsulation (45.5 ± 0.6% w/v) of these polymeric nanoparticles was high, and their components were evaluated using spectroscopy. UV–VIS, FTIR and DSC showed that all of the nanoparticles contained the desired components, and these compounds interacted to form a nanocomposite. Using the agar diffusion method and live/dead bacterial viability assays, we demonstrated that these nanoparticles have antimicrobial properties against Escherichia coli, and they retain their magnetic properties as measured using a vibrating sample magnetometer (VSM). Cytotoxicity was assessed in HepG2 cells using live/dead viability assays and MTS, and these assays showed low cytotoxicity with IC50 > 10 mg/mL nanoparticles.
Our results indicate that hybrid and multifunctional PHBV/SPION/CEF nanoparticles are suitable as a superparamagnetic drug delivery system that can guide, concentrate and site–specifically release drugs with antibacterial activity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12951-015-0077-5) contains supplementary material, which is available to authorized users.
PHBV; SPION; Ceftiofur; Polymeric nanoparticles; Drug delivery; Superparamagnetic nanoparticles
The shape of plasmonic nanostructures such as silver and gold is vital to their physical and chemical properties and potential applications. Recently, preparation of complex nanostructures with rich function by chemical multistep methods is the hotspot of research. In this review we introduce three typical multistep methods to prepare silver nanostructures with well-controlled shapes, including the double reductant method, etching technique and construction of core-shell nanostructures. The growth mechanism of double the reductant method is that different favorable facets of silver nanocrystals are produced in different reductants, which can be used to prepare complex nanostructures such as nanoflags with ultranarrow resonant band bandwidth or some silver nanostructures which are difficult to prepare using other methods. The etching technique can selectively remove nanoparticles to achieve the aim of shape control and is widely used for the synthesis of nanoflowers and hollow nanostructures. Construction of core-shell nanostructures is another tool to control shape and size. The three methods can not only prepare various silver nanostructures with well-controlled shapes, which exhibit unique optical properties, such as strong surface-enhanced Raman scattering (SERS) signal and localized surface plasmon resonance (LSPR) effect, but also have potential application in many areas.
reductant; nanoparticle etching; composited nanostructures; shape control; plasmonic sensors
Hybrid nanostructures with unique optical and magnetic properties have attracted considerable interest as effective mediators for medical imaging and therapy. An aqueous-based, self-assembly approach to synthesizing hybrid plasmonic-superparamagnetic nanostructures is presented. The building blocks of the hybrid nanostructure include plasmonic gold nanorods (AuNRs) and superparamagnetic iron oxide nanoparticles (SPIONs). The AuNRs were functionalized via carboxyl-bearing surface ligands, while the SPIONs were kept “bare” after synthesis via a surfactant-free, thermal decomposition reaction in triethylene glycol. Hybrid SPION-studded AuNR nanostructures were produced upon simple mixing of the components due to chemisorption of the AuNRs’ free carboxyl groups to the SPIONs’ surfaces. The reported synthesis strategy is modular in nature and can be expanded to build hybrid nanostructures with a multitude of other plasmonic nanoparticles. With tunable near-infrared absorption peaks and a sufficient number of bound SPIONs, the self-assembled hybrid nanostructures are suitable for biomedical imaging and therapy applications.
Hybrid nanostructures; self-assembly; gold nanoparticles; iron oxide; silica; plasmonic nanoparticles; superparamagnetic nanoparticles
When X-rays irradiate radioluminescence nanoparticles, they generate visible and near infrared light that can penetrate through centimeters of tissue. X-ray luminescence tomography (XLT) maps the location of these radioluminescent contrast agents at high resolution by scanning a narrow X-ray beam through the tissue sample and collecting the luminescence at every position. Adding magnetic functionality to these radioluminescent particles would enable them to be guided, oriented, and heated using external magnetic fields, while their location and spectrum could be imaged with XLT and complementary magnetic resonance imaging. In this work, multifunctional monodispersed magnetic radioluminescent nanoparticles were developed as potential drug delivery carriers and radioluminescence imaging agents. The particles consisted of a spindle-shaped magnetic γ-Fe2O3 core and a radioluminescent europium-doped gadolinium oxide shell. Particles with solid iron oxide cores displayed saturation magnetizations consistent with their ~13% core volume, however, the iron oxide quenched their luminescence. In order to increase the luminescence, we partially etched the iron oxide core in oxalic acid while preserving the radioluminescent shell. The core size was controlled by the etching time which in turn affected the particles’ luminescence and magnetic properties. Particles with intermediate core sizes displayed both strong magnetophoresis and luminescence properties. They also served as MRI contrast agents with relaxivities of up to 58 mM−1s−1 (r2) and 120 mM−1s−1 (r2*). These particles offer promising multimodal MRI/fluorescence/X-ray luminescence contrast agents. Our core-shell synthesis technique offers a flexible method to control particle size, shape, and composition for a wide range of biological applications of magnetic/luminescent nanoparticles.
Gold nanostructures have garnered considerable attention in recent years for their potential to enhance both the diagnosis and treatment of cancer through their advantageous chemical and physical properties. The key feature of Au nanostructures for enabling this diverse array of biomedical applications is their attractive optical properties, i.e. the scattering and absorption of light at resonant wavelengths due to the excitation of plasmon oscillations. This phenomenon is commonly known as localized surface plasmon resonance (LSPR) and is the source of the ruby red color of conventional Au colloids. The resonant wavelength is highly dependent on the size, shape, and geometry of the nanostructures, providing a set of knobs to maneuver the optical properties as needed. For in vivo applications, especially when optical excitation or transduction is involved, the LSPR peaks of the Au nanostructures have to be tuned to the transparent window of soft tissues in the near-infrared (NIR) region (from 700–900 nm) in order to maximize the penetration depth.
One class of nanostructures with tunable LSPR peaks in the NIR region is Au nanocages. These versatile nanostructures are characterized by hollow interiors, ultrathin and porous walls, and can be prepared in relatively large quantities using a remarkably simple procedure based on the galvanic replacement between Ag nanocubes and aqueous chloroauric acid. The LSPR peaks of Au nanocages can be readily and precisely tuned to any wavelength in the NIR region by controlling their size and/or wall thickness. Other significant features of Au nanocages that make them particularly intriguing materials for biomedical applications include their compact sizes, large absorption cross sections (almost five orders of magnitude greater than those of conventional organic dyes), bio-inertness, as well as a robust and straightforward procedure for surface modification based on the Au-thiolate chemistry. In this article, we present some of the most recent advances in the use of Au nanocages for a broad range of theranostic applications, including their use: i) as tracers for tracking by multi-photon luminescence; ii) as contrast agents for photoacoustic (PA) and mutimodal (PA/fluorescence) imaging; iii) as photothermal agents for the selective destruction of cancerous or diseased tissue; and iv) as drug delivery vehicles for controlled and localized release in response to external stimuli such as NIR radiation or high-intensity focused ultrasound (HIFU).
In this article, we reported the near-field interactions between the Ru(bpy)32+ complexes and plasmon resonances from the bimetallic nanoshells. The metallic nanoshells were fabricated on 20 nm silica spheres as cores by depositing 10 nm monometallic or bimetallic shells. There were approx. 15 Ru(bpy)32+ complexes in the silica core. The metal shells were constituted of silver or/and gold. The bimetallic shells could be generated in homogeneous or heterogeneous geometries. The homogeneous bimetallic shells contained 10 nm silver-gold alloys. The heterogeneous bimetallic shells contained successive 5 nm gold and 5 nm silver shells, or alternatively, 5 nm silver and 5 nm gold shells. Optical properties of metal nanoshells were studied on both the ensemble spectra and single nanoparticle imaging measurements. The heterogeneous bimetallic shells were found to have a large scale of metal-enhanced emission relative to the monometallic or homogeneous bimetallic shells. It is because the heterogeneous bimetallic shells may display split dual plasmon resonances which can interact with the excitation and emission bands of the Ru(bpy)32+ complexes in the silica cores leading to more efficient near-field interactions. The prediction can be demonstrated by the lifetimes. Therefore, it is suggested that both the compositions and geometries of the metal shells can influence the interactions with the fluorophores in the cores. This observation also offers us an opportunity for developing plasmon-based fluorescence metal nanoparticles as novel nanoparticle imaging agents which have high performances in fluorescence cell or tissue imaging.
fluorescence; bimetallic nanoshell; plasmon resonance; Ru(bpy)32+ complexes; optical properties of single nanoparticle; time-resolved confocal microscope; and near-field interaction
Fe3O4-gold-chitosan core-shell nanostructure can be used in biotechnological and biomedical applications such as magnetic bioseparation, water and wastewater treatment, biodetection and bioimaging, drug delivery, and cancer treatment.
Magnetite nanoparticles with an average size of 9.8 nm in diameter were synthesized using the chemical co-precipitation method. A gold-coated Fe3O4 monotonous core-shell nanostructure was produced with an average size of 15 nm in diameter by glucose reduction of Au3+ which is then stabilized with a chitosan cross linked by formaldehyde. The results of analyses with X-ray diffraction (XRD), Fourier Transformed Infrared Spectroscopy (FTIR), Transmission Electron Microscopy (TEM), and Atomic Force Microscopy (AFM) indicated that the nanoparticles were regularly shaped, and agglomerate-free, with a narrow size distribution.
A rapid, mild method for synthesizing Fe3O4-gold nanoparticles using chitosan was investigated. A magnetic core-shell-chitosan nanocomposite, including both the supermagnetic properties of iron oxide and the optical characteristics of colloidal gold nanoparticles, was synthesized.
bioseparation; core-shell; Fe3O4-gold-chitosan; hydrogel; magnetic; nanocomposite; nanoparticle
Externally modulated nanoparticles comprise a rapidly advancing class of cancer nanotherapeutics, which combine the favorable tumor accumulation of nanoparticles, with external spatio-temporal control on therapy delivery via optical, magnetic, or ultrasound modalities. The local control on therapy enables higher tumor treatment efficacy, while simultaneously reducing off-target effects. The nanoparticle interactions with external fields have an additional advantage of frequently generating an imaging signal, and thus such agents provide theranostic (both diagnostic and therapeutic) capabilities. In this review, we classify the emerging externally modulated theranostic nanoparticles according to the mode of external control and describe the physiochemical mechanisms underlying the external control of therapy, and illustrate the major embodiments of nanoparticles in each class with proven biological efficacy: (I) electromagnetic radiation in visible and near-infrared range is being exploited for gold based and carbon nanostructures with tunable surface plasmon resonance (SPR) for imaging and photothermal therapy (PTT) of cancer, photochemistry based manipulations are employed for light sensitive liposomes and porphyrin based nanoparticles; (II) Magnetic field based manipulations are being developed for iron-oxide based nanostructures for magnetic resonance imaging (MRI) and magnetothermal therapy; (III) ultrasound based methods are primarily being employed to increase delivery of conventional drugs and nanotherapeutics to tumor sites.
Cancer nanotechnology; theranostics; hyperthermia; NIR therapy; gold nanoparticles (AuNPs)
Plasmon-resonant gold nanostars (NSTs) with magnetic cores were synthesized by a multistep sequence from superparamagnetic Fe3O4 nanoparticles (NPs), and evaluated as optical contrast agents under magnetomotive (MM) imaging conditions. Core–shell Fe3O4@Au NPs were prepared in nonpolar organic solvents with nanometer control over shell thickness, and with good epitaxy to the Fe3O4 surface. Anisotropic growth was performed in micellar solutions of cetyltrimethylammonium bromide (CTAB) under mildly reducing conditions, resulting in NSTs with physical features similar to those produced from colloidal gold seeds. NSTs could be produced below 100 nm from tip to tip but seed size had a significant impact on growth habit, with larger seed particles producing submicron-sized “morning stars.” Both NSTs and aggregated core–shell NPs are responsive to in-plane magnetic field gradients and can provide enhanced near-infrared (NIR) contrast under MM conditions, but do so by different mechanisms. NSTs can modulate polarized NIR scattering with minimal translational motion, giving the appearance of a periodic but stationary “blinking,” whereas core–shell NP aggregates require lateral displacement for signal modulation. The polarization-sensitive MM imaging modality offers the dual advantage of enhanced signal quality and reduced background signal, and can be applied toward the detection of magnetomotive NSTs in heterogenous biological samples, as illustrated by their detection inside of granular cells such as macrophages.
imaging; magnetic nanoparticles; nanomedicine; nanostars; plasmonics; synthesis
Near infrared absorbing plasmonic nanoparticles enhance photothermal therapy of tumors. In this procedure, systemically delivered gold nanoparticles preferentially accumulate at the tumor site and when irradiated using laser light, produce localized heat sufficient to damage tumor cells. Gold nanoshells and nanorods have been widely studied for this purpose, and while both exhibit strong NIR absorption, their overall absorption and scattering properties differ widely due to their geometry. In this paper, we compared the photothermal response of both nanoparticle types including the heat generation and photothermal efficiency.
Tissue simulating phantoms, with varying concentrations of gold nanoparticles, were irradiated with a near-infrared diode laser while concurrently monitoring the surface temperature with an infrared camera. We calculated nanoshell and nanorod optical properties using the Mie solution and the discrete dipole approximation, respectively. In addition, we measured the heat generation of nanoshells and nanorods at the same optical density to determine the photothermal transduction efficiency for both nanoparticle types.
We found that the gold nanoshells produced more heat than gold nanorods at equivalent number densities (# of nanoparticles/mL), whereas the nanorods generated more heat than nanoshells at equivalent extinction values at the irradiance wavelength. To reach an equivalent heat generation, we found that it was necessary to have ~36x more nanorods than nanoshells. However, the gold nanorods were found to have two times the photothermal transduction efficiency than the gold nanoshells.
For the NPs tested, the nanoshells generated more heat, per nanoparticle, than nanorods, primarily due to their overall larger geometric cross section. Conversely, we found that the gold nanorods had a higher photothermal efficiency than the gold nanoshells. In conclusion, the ideal choice of plasmonic nanoparticle requires not only per particle efficiency, but also the in vivo particle targeting ability under study.
Cancer; Gold Nanorods; Gold Nanoshells; Infrared Imaging; Photothermal Therapy; Photothermal Efficiency
Multifunctional nanomaterials with unique magnetic and luminescent properties have broad potential in biological applications. Because of the overexpression of vascular cell adhesion molecule-1 (VCAM-1) receptors in inflammatory endothelial cells as compared with normal endothelial cells, an anti-VCAM-1 monoclonal antibody can be used as a targeting ligand. Herein we describe the development of multifunctional core-shell Fe3O4@SiO2 nanoparticles with the ability to target inflammatory endothelial cells via VCAM-1, magnetism, and fluorescence imaging, with efficient magnetic resonance imaging contrast characteristics. Superparamagnetic iron oxide and fluorescein isothiocyanate (FITC) were loaded successfully inside the nanoparticle core and the silica shell, respectively, creating VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles that were characterized by scanning electron microscopy, transmission electron microscopy, fluorescence spectrometry, zeta potential assay, and fluorescence microscopy. The VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles typically had a diameter of 355 ± 37 nm, showed superparamagnetic behavior at room temperature, and cumulative and targeted adhesion to an inflammatory subline of human umbilical vein endothelial cells (HUVEC-CS) activated by lipopolysaccharide. Further, our data show that adhesion of VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles to inflammatory HUVEC-CS depended on both shear stress and duration of exposure to stress. Analysis of internalization into HUVEC-CS showed that the efficiency of delivery of VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles was also significantly greater than that of nontargeted Fe3O4@SiO2(FITC)-NH2 nanoparticles. Magnetic resonance images showed that the superparamagnetic iron oxide cores of the VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles could also act as a contrast agent for magnetic resonance imaging. Taken together, the cumulative adhesion and uptake potential of these VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles targeted to inflammatory endothelial cells could be used in the transfer of therapeutic drugs/genes into these cells or for diagnosis of vascular disease at the molecular and cellular levels in the future.
silica nanoparticles; vascular cell adhesion molecule-1; endothelial cells; adhesion; magnetic resonance imaging
A metal shell was used in this study to provide significant enhancement of the up-converted emission from cubic NaYF4 nanoparticles, creating a valuable composite material for labeling in biology and other applications – use of the cubic form of the material obviates the need to undertake a high temperature transformation to the naturally more efficient hexagonal phase. The NaYF4 matrix contained ytterbium sensitizer and an Erbium (Er) or Thulium (Tm) activator. The particle sizes of the as-synthesized nanoparticles were in the range of 20–40 nm with a gold shell thickness of 4–8 nm. The gold shell was macroscopically amorphous. The synthesis method was based on a citrate chelation. In this approach, we exploited the ability of the citrate ion to act as a reductant and stabilizer. Confining the citrate ion reductant on the nanophosphor surface rather than in the solution was critical to the gold shell formation. The plasmonic shell enhanced the up-conversion emission of Tm from visible and near-infrared regions by up to a factor of 8, in addition to imparting a visible color arising from the plasmon absorption of the gold shell. The up-conversion enhancement observed with Tm and Er were different for similar gold coverages, with local crystal field changes as a possible route to enhance up-conversion emission from high symmetry structural hosts. These novel up-converting nanophosphor particles combine the phosphor and features of a gold shell, providing a unique platform for many biological imaging and labeling applications.
Cubic-NaYF4; Up-converting nanophosphor; Citrate method; Gold coating; Up-conversion emission; Plasmonic enhancement
The optical properties of multi-functionalized cobalt ferrite (CoFe2O4), cobalt zinc ferrite (Co0.5Zn0.5Fe2O4), and zinc ferrite (ZnFe2O4) nanoparticles have been enhanced by coating them with silica shell using a modified Stöber method. The ferrites nanoparticles were prepared by a modified citrate gel technique. These core/shell ferrites nanoparticles have been fired at temperatures: 400°C, 600°C and 800°C, respectively, for 2 h. The composition, phase, and morphology of the prepared core/shell ferrites nanoparticles were determined by X-ray diffraction and transmission electron microscopy, respectively. The diffuse reflectance and magnetic properties of the core/shell ferrites nanoparticles at room temperature were investigated using UV/VIS double-beam spectrophotometer and vibrating sample magnetometer, respectively. It was found that, by increasing the firing temperature from 400°C to 800°C, the average crystallite size of the core/shell ferrites nanoparticles increases. The cobalt ferrite nanoparticles fired at temperature 800°C; show the highest saturation magnetization while the zinc ferrite nanoparticles coated with silica shell shows the highest diffuse reflectance. On the other hand, core/shell zinc ferrite/silica nanoparticles fired at 400°C show a ferromagnetic behavior and high diffuse reflectance when compared with all the uncoated or coated ferrites nanoparticles. These characteristics of core/shell zinc ferrite/silica nanostructures make them promising candidates for magneto-optical nanodevice applications.
nanostructures; oxides; cobalt ferrite; cobalt zinc ferrite; zinc ferrite; magnetic properties; diffuse reflectance.
Nanoparticles with gold shell and iron core have unique optical and magnetic properties which can be utilized for simultaneous detection and treatment strategies. Several nanoparticles have been synthesized and shown to mediate a variety of potential applications in biomedicine, including cancer molecular optical and magnetic resonance imaging, controlled drug delivery, and photothermal ablation therapy. However, to be effective, these nanoparticles must be delivered efficiently into their targets. In this review, we will provide an updated summary of the gold-shelled magnetic nanoparticles that have been synthesized, methods for characterization, and their potential for cancer diagnosis and treatment. We will also discuss the biological barriers that need to be overcome for the effective delivery of these nanoparticles. The desired nanoparticle characteristics needed to evade these biological barriers were also explained. Hopefully, this review will help researchers in designing nanoparticles by carefully choosing the optimum size, shape, surface charge, and surface coating.
We demonstrate top-down synthesis of monodisperse plasmonic nanoparticles designed to contain internal Raman hot spots. Our Raman-active nanoparticles are fabricated using nanoimprint lithography and thin-film deposition and are composed of novel internal structures with sublithographic dimensions: a disk-shaped Ag core, a Petri-dish-shaped SiO2 base whose inner surface is coated with Ag film, and a sub-10 nm scale circular gap between the core and the base. Confocal Raman measurements and electromagnetic simulations show that Raman hot spots appear at the inside perimeter of individual nanoparticles and serve as the source of a 1000-fold improvement of minimum molecular detection level that enables detection of signals from a few molecules near hot spots. A multimodality version of these nanoparticles, which includes the functionality offered by magnetic multilayers, is also demonstrated. These results illustrate the potential of direct fabrication for creating exotic monodisperse nanoparticles, which combine engineered internal nanostructures and multilayer composite materials, for use in nanoparticle-based molecular imaging and detection.
surface-enhanced Raman scattering; plasmonic; nanoparticle; magnetic
Gold (Au) nanoshells with solid silica cores have great potential for cancer photothermal therapy. However, this nanostructure cannot carry enough drugs. Here, we report a Au nanoshell with a hollow silica core for drug loading and cancer therapy. The silica shells were synthesized using nanoliposome templates, and then Au nanoshells were grown on the outer surface of the silica shells. Transmission-electron and scanning-electron microscopy showed that the Au nanoshells were successfully fabricated, and that the liposome/SiO2/Au core-shell nanocomposites were spherical with a narrow size distribution. Images of several broken spheres, and the fact that hollow templates (liposomes) were used, suggest that the fabricated Au nanoshells were hollow. After doxorubicin (DOX) was incorporated into liposome/SiO2/Au, the DOX-loaded Au nanoshells killed cancer cells with high therapeutic efficacy when irradiated with near-infrared light, suggesting that the Au nanoshells delivered both DOX chemotherapy and photothermal therapy with a synergistic effect.
gold nanoshell; liposome template; synthesis; doxorubicin; cancer therapy
Hybrid plasmonic-magnetic nanoparticles possess properties that are attractive in bioimaging, targeted drug delivery, in vivo diagnosis and therapy. The stability and toxicity, however, of such nanoparticles challenge their safe use today. Here, biocompatible, SiO2-coated, Janus-like Ag/Fe2O3 nanoparticles are prepared by one-step, scalable flame aerosol technology. A nanothin SiO2 shell around these multifunctional nanoparticles leaves intact their morphology, magnetic and plasmonic properties but minimizes the release of toxic Ag+ ions from the nanosilver surface and its direct contact with live cells. Furthermore, this silica shell hinders flocculation and allows for easy dispersion of such nanoparticles in aqueous and biological buffer (PBS) solutions without any extra functionalization step. As a result, these hybrid particles exhibited no cytotoxicity during bioimaging and remained stable in suspension with no signs of agglomeration and sedimentation or settling. Their performance as biomarkers was explored by selectively binding them with live tagged Raji and HeLa cells enabling their detection under dark-filed illumination. Therefore, these SiO2-coated Ag/Fe2O3 nanoparticles do not exhibit the limiting physical properties of each individual component but retain their desired functionalities facilitating thus, the safe use of such hybrid nanoparticles in bio-applications.
silver; iron oxide; silicon dioxide; cancer cell detection; heterodimer
Understanding the correlation between physicochemical properties and morphology of nanostructures is a prerequisite for widespread applications of nanomaterials in environmental application areas. Herein, we illustrated that the uniform-sized SnO2@C hollow nanoparticles were large-scale synthesized by a facile hydrothermal method. The size of the core-shell hollow nanoparticles was about 56 nm, and the shell was composed of a solid carbon layer with a thickness of 2 ~ 3 nm. The resulting products were characterized in terms of morphology, composition, and surface property by various analytical techniques. Moreover, the SnO2@C hollow nanoparticles are shown to be effective adsorbents for removing four different dyes from aqueous solutions, which is superior to the pure hollow SnO2 nanoparticles and commercial SnO2. The enhanced mechanism has also been discussed, which can be attributed to the high specific surface areas after carbon coating.
Tin oxide; Carbon coating; Core-shell; Dye removal
Heterojunctions near infrared (NIR) photodetectors have attracted increasing research interests for their wide-ranging applications in many areas such as military surveillance, target detection, and light vision. A high-performance NIR light photodetector was fabricated by coating the methyl-group terminated Si nanowire array with plasmonic gold nanoparticles (AuNPs) decorated graphene film. Theoretical simulation based on finite element method (FEM) reveals that the AuNPs@graphene/CH3-SiNWs array device is capable of trapping the incident NIR light into the SiNWs array through SPP excitation and coupling in the AuNPs decorated graphene layer. What is more, the coupling and trapping of freely propagating plane waves from free space into the nanostructures, and surface passivation contribute to the high on-off ratio as well.