Photothermal ablation is a minimally invasive approach, which typically involves delivery of photothermal sensitizers to targeted tissues. The purpose of our study was to demonstrate that gold nanoparticles are phagocytosed by pancreatic cancer cells, thus permitting magnetic resonance imaging (MRI) of sensitizer delivery and photothermal ablation.
Patients and methods
Iron-oxide core/gold-shell nanoparticles (GoldMag®, 30 nm diameter; Xi’an GoldMag Biotechnology Co, Xi’an, People’s Republic of China) were used. In a 96-well plate, 3 × 104 PANC-1 (human pancreatic cancer cell line) cells were placed. GoldMag (0, 25, or 50 μg/mL) was added to each well and 24 hours allowed for cellular uptake. Samples were then divided into two groups: one treated with photothermal ablation (7.9 W/cm2) for 5 minutes, the other not treated. Photothermal ablation was performed using laser system (BWF5; B&W Tek, Inc, Newark, DE, USA). Intraprocedural temperature changes were measured using a fiber optic temperature probe (FTP-LN2; Photon Control Inc, Burnaby, BC, Canada). After 24 hours, the remaining number of viable cells was counted using trypan blue staining; cell proliferation percentage was calculated based on the total number of viable cells after treatment compared with control. MRI of GoldMag uptake was performed using a 7.0T ClinScan system (Bruker BioSpin, Ettlingen, Germany).
Temperature curves demonstrated that with increased GoldMag uptake, laser irradiation produced higher temperature elevations in the corresponding samples; temperature elevations of 12.89°C, 35.16°C, and 79.51°C were achieved for 0, 25, and 50 μg/mL GoldMag. Without photothermal ablation, the cell proliferation percentage changed from 100% to 71.3% and 47.0% for cells treated with 25 and 50 μg/mL GoldMag. Photothermal ablation of PANC-1 cells demonstrated an effective treatment response, specifically a reduction to only 61%, 21.9%, and 2.3% cell proliferation for cells treated with 0, 25, and 50 μg/mL GoldMag. MRI was able to visualize GoldMag uptake within PANC-1 cells.
Our findings suggest that photothermal ablation may be effective in the treatment of pancreatic cancer. GoldMag nanoparticles could serve as photothermal sensitizers, and MRI is feasible to quantify delivery.
photothermal ablation therapy; hybrid nanoparticles; magnetic resonance imaging
Functionalized gold nanoparticles with controlled geometrical and optical properties are the subject of intensive studies and biomedical applications, including genomics, biosensorics, immunoassays, clinical chemistry, laser phototherapy of cancer cells and tumors, the targeted delivery of drugs, DNA and antigens, optical bioimaging and the monitoring of cells and tissues with the use of state-of-the-art detection systems. This work will provide an overview of the recent advances and current challenges facing the biomedical application of gold nanoparticles of various sizes, shapes, and structures. The review is focused on the application of gold nanoparticle conjugates in biomedical diagnostics and analytics, photothermal and photodynamic therapies, as a carrier for delivering target molecules, and on the immunological and toxicological properties. Keeping in mind the huge volume and high speed of the data update rate, 2/3 of our reference list (certainly restricted to 250 Refs.) includes publications encompassing the past 5 years.
gold nanoparticles; plasmon resonance; biosensors; biomedical diagnostics; photothermal and photodynamic therapy; targeted drug delivery; nanotoxicology
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
As applications of nanoparticles in medical imaging and biomedicine rapidly expand, the interactions of nanoparticles with living cells have become an area of active interest. For example, intracellular trafficking of nanoparticles – an important part of cell-nanoparticle interaction, has been well studied using plasmonic nanoparticles and optical or optics-based techniques due to the change in optical properties of the nanoparticle aggregates. However, magnetic nanoparticles, despite their wide range of clinical applications, do not exhibit plasmonic-resonant properties and therefore their intracellular aggregation cannot be detected by optics-based imaging techniques. In this study, we investigated the feasibility of a novel imaging technique – pulsed magneto-motive ultrasound (pMMUS), to identify intracellular trafficking of endocytosed magnetic nanoparticles. In pulsed magneto-motive ultrasound imaging a focused, high intensity, pulsed magnetic field is used to excite the cells labeled with magnetic nanoparticles, and ultrasound imaging is then used to monitor the mechanical response of the tissue. We demonstrated previously that clusters of magnetic nanoparticles amplify the pMMUS signal in comparison to signal from individual nanoparticles. Here we further demonstrate that pMMUS imaging can identify interaction between magnetic nanoparticles and living cells, i.e. intracellular aggregation of nanoparticles within the cells. The results of our study suggest that pMMUS imaging can not only detect the presence of magnetic nanoparticles but also provides information about their intracellular trafficking non-invasively and in real-time.
Pulsed magneto-motive ultrasound imaging; superparamagnetic iron-oxide nanoparticles; macrophage; endocytosis; intracellular trafficking
Contrast in optical coherence tomography (OCT) images can be enhanced by utilizing surface plasmon resonant gold nanoparticles. To improve the poor in vivo transport of gold nanoparticles through biological barriers, an efficient delivery strategy is needed. In this study, the improved penetration and distribution of gold nanoparticles were achieved by microneedle and ultrasound, respectively, and it was demonstrated that this multimodal delivery of antibodyconjugated PEGylated gold nanoparticles enhanced the contrast in in vivo OCT images of oral dysplasia in a hamster model.
optical coherence tomography; optical contrast agent; gold nanoparticles; enhanced delivery; ultrasound; microneedles
Recent advances in nanotechnology have resulted in the manufacture of a plethora of nanoparticles with different sizes, shapes, core physicochemical properties and surface modifications that are being investigated for potential medical applications, particularly for the treatment of cancer. This review focuses on the therapeutic use of customized gold nanoparticles, magnetic nanoparticles and carbon nanotubes that efficiently generate heat upon electromagnetic (light and magnetic fields) stimulation after direct injection into tumors or preferential accumulation in tumors following systemic administration. This review will also focus on the evolving strategies to improve the therapeutic index of prostate cancer treatment using nanoparticle-mediated hyperthermia.
Nanoparticle-mediated thermal therapy is a new and minimally invasive tool in the armamentarium for the treatment of cancers. Unique challenges posed by this form of hyperthermia include the non-target biodistribution of nanoparticles in the reticuloendothelial system when administered systemically, the inability to visualize or quantify the global concentration and spatial distribution of these particles within tumors, the lack of standardized thermal modeling and dosimetry algorithms, and the concerns regarding their biocompatibility. Nevertheless, novel particle compositions, geometries, activation strategies, targeting techniques, payload delivery strategies, and radiation dose enhancement concepts are unique attributes of this form of hyperthermia that warrant further exploration. Capitalizing on these opportunities and overcoming these challenges offers the possibility of seamless and logical translation of this nanoparticle-mediated hyperthermia paradigm from the bench to the bedside.
Nanoparticles; magnetic; optical; activatable; hyperthermia; prostate cancer
Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important chapter of nanomedicine. Nanobiotechnology has refined and extended the limits of molecular diagnosis of cancer, for example, through the use of gold nanoparticles and quantum dots. Nanobiotechnology has also improved the discovery of cancer biomarkers, one such example being the sensitive detection of multiple protein biomarkers by nanobiosensors. Magnetic nanoparticles can capture circulating tumor cells in the bloodstream followed by rapid photoacoustic detection. Nanoparticles enable targeted drug delivery in cancer that increases efficacy and decreases adverse effects through reducing the dosage of anticancer drugs administered. Nanoparticulate anticancer drugs can cross some of the biological barriers and achieve therapeutic concentrations in tumor and spare the surrounding normal tissues from toxic effects. Nanoparticle constructs facilitate the delivery of various forms of energy for noninvasive thermal destruction of surgically inaccessible malignant tumors. Nanoparticle-based optical imaging of tumors as well as contrast agents to enhance detection of tumors by magnetic resonance imaging can be combined with delivery of therapeutic agents for cancer. Monoclonal antibody nanoparticle complexes are under investigation for diagnosis as well as targeted delivery of cancer therapy. Nanoparticle-based chemotherapeutic agents are already on the market, and several are in clinical trials. Personalization of cancer therapies is based on a better understanding of the disease at the molecular level, which is facilitated by nanobiotechnology. Nanobiotechnology will facilitate the combination of diagnostics with therapeutics, which is an important feature of a personalized medicine approach to cancer.
This paper describes the synthesis and surface engineering of core/shell-type iron/iron oxide nanoparticles for magnetic hyperthermia cancer therapy. Iron/iron oxide nanoparticles were synthesized from microemulsions of NaBH4 and FeCl3, followed by surface modification in which a thin hydrophobic hexamethyldisilazane layer - used to protect the iron core - replaced the CTAB coating on the particles. Phosphatidylcholine was then assembled on the nanoparticle surface. The resulting nanocomposite particles have a biocompatible surface and show good stability in both air and aqueous solution. Compared to iron oxide nanoparticles, the nanocomposites show much better heating in an alternating magnetic field. They are good candidates for both hyperthermia and magnetic resonance imaging applications.
(i) Importance of the field
Plasmonic nanoparticles provide a novel route to treat cancer due to their ability to effectively convert light into heat for photothermal destruction. Combined with the targeting mechanisms possible with nanoscale materials, this technique has the potential to enable highly targeted therapies to minimize undesirable side effects.
(ii) Areas covered in this review
This review discusses the use of gold nanocages, a novel class of plasmonic nanoparticles, for photothermal applications. Gold nanocages are hollow, porous structures with compact sizes, precisely controlled plasmonic properties and surface chemistry. Additionally, we discuss a recent study of gold nanocages as drug-release carriers by externally controlling the opening and closing of the pores with a smart polymer whose conformation changes at a specific temperature. Release of the contents can be initiated remotely through near-infrared irradiation. Together, these topics cover the years from 2002-2009.
(iii) What the reader will gain
The reader will be exposed to different aspects of gold nanocages, including synthesis, surface modification, in vitro studies, intial in vivo data, and perspectives on future studies.
(iv) Take home message
Gold nanocages are a promising platform for cancer therapy in terms of both photothermal destruction and drug delivery.
photothermal therapy; drug delivery; nanotechnology; nanomedicine
The propensity of nanoparticles to aggregate in aqueous media hinders their effective use in biomedical applications. Gold nanorods (GNRs) have been investigated as therapeutics, imaging agents, and diagnostics. We report that chemically generated gold nanorods rapidly aggregate in biologically relevant media. Depositing polyelectrolyte multilayers on gold nanorods enhanced the stability of these nanoparticles for at least up to four weeks. Dispersions of polyelectrolyte (PE)-gold nanorod assemblies (PE-GNRs) demonstrate a stable Arrhenius-like photothermal response, which was exploited for the hyperthermic ablation of prostate cancer cells in vitro. Sub-toxic concentrations of PE-GNR assemblies were also employed for delivering exogenous plasmid DNA to prostate cancer cells. PE-GNRs based on a cationic polyelectrolyte recently synthesized in our laboratory demonstrated higher transfection efficacy and lower cytotoxicity compared to those based on polyethyleneimine, a current standard for polymer-mediated gene delivery. Our results indicate that judicious engineering of biocompatible polyelectrolytes leads to multifunctional gold nanorod-based assemblies that combine high stability and low cytotoxicity with photothermal ablation, gene delivery, and optical imaging capabilities on a single platform.
gold nanorods; stability; photothermal; near infrared; polyelectrolytes; cationic polymers; non viral gene delivery; hyperthermia
Topical or transdermal drug delivery is challenging because the skin acts as a natural and protective barrier. Therefore, several methods have been examined to increase the permeation of therapeutic molecules into and through the skin. One approach is to use the nanoparticulate delivery system. Starting with liposomes and other vesicular systems, several other types of nanosized drug carriers have been developed such as solid lipid nanoparticles, nanostructured lipid carriers, polymer-based nanoparticles and magnetic nanoparticles for dermatological applications. This review article discusses how different particulate systems can interact and penetrate into the skin barrier. In this review, the effectiveness of nanoparticles, as well as possible mode of actions of nanoparticles, is presented. In addition to nanoparticles, cell-penetrating peptide (CPP)-mediated drug delivery into the skin and the possible mechanism of CPP-derived delivery into the skin is discussed. Lastly, the effectiveness and possible mechanism of CPP-modified nanocarriers into the skin are addressed.
Topical and transdermal skin delivery; nanoparticles; cell-penetrating peptides
Site-specific delivery of nanoparticles poses a significant challenge, especially in the brain where the blood–brain barrier prevents the entry of most therapeutic compounds including nanoparticle-based anti-cancer agents. In this context, the use of macrophages as vectors for the delivery of gold–silica nanoshells to infiltrating gliomas will be reviewed in this article. Gold–silica nanoshells are readily phagocytosed by macrophages without any apparent toxic effects, and the results of in vitro studies have demonstrated the migratory potential of nanoshell-loaded macrophages in human glioma spheroids. Of particular interest is the observation that, after near-infrared exposure of spheroids containing nanoshell-loaded macrophages, sufficient heat was generated to suppress spheroid growth. Collectively, these findings demonstrate the potential of macrophages as nanoshell delivery vectors for photothermal therapy of gliomas, and they certainly provide the basis for future animal studies.
Macrophages; Nanoparticles; Gold–silica nanoshells; Gliomas; Spheroids; Blood–brain barrier
In recent times, nanofluids have been studied by their thermal properties due to their variety of applications that range from photothermal therapy and radiofrequency hyperthermia (which have proven their potential use as coadjutants in these medical treatments for cancer diseases) to next-generation thermo-fluids. In this work, photoacoustic spectroscopy for a specific study of thermal diffusivity, as a function of particle size and concentration, on colloidal water-based gold nanofluids is reported. Gold nanoparticles were synthetized in the presence of hydroquinone through a seed-mediated growth with homogenous sizes and shapes in a range of 16 to 125 nm. The optical response, size and morphology of these nanoparticles were characterized using ultraviolet–visible spectroscopy and transmission electron microscopy, respectively. Thermal characterizations show a decrease in the thermal diffusivity ratio as the nanoparticle size is increased and an enhancement in thermal diffusivity ratio as nanoparticle concentration is added into the nanofluids. Compared with other techniques in the literature such as thermal lens and hot wire method, this photoacoustic technique shows an advantage in terms of precision, and with a small amount of sample required (500 μl), this technique might be suitable for the thermal diffusivity measurement of nanofluids. It is also a promising alternative to classical techniques.
Gold nanoparticles; Nanofluids; Photoacoustic; Thermal diffusivity
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
Nanoparticle technology is being incorporated into many areas of molecular science and biomedicine. Because nanoparticles are small enough to enter almost all areas of the body, including the circulatory system and cells, they have been and continue to be exploited for basic biomedical research as well as clinical diagnostic and therapeutic applications. For example, nanoparticles hold great promise for enabling gene therapy to reach its full potential by facilitating targeted delivery of DNA into tissues and cells. Substantial progress has been made in binding DNA to nanoparticles and controlling the behavior of these complexes. In this article, we review research on binding DNAs to nanoparticles as well as our latest study on non-viral gene delivery using polyethylenimine-coated magnetic nanoparticles.
magnetic nanoparticles; Magnetofection; gene delivery; polyethylenimine
For biomedical applications, emerging nanostructures requires stringent evaluations for their biocompatibility. Core/shell iron/carbon nanoparticles (Fe@CNPs) are nanomaterials that have potential applications in magnetic resonance imaging (MRI), magnetic hyperthermia and drug delivery. However, their interactions with biological systems are totally unknown. To evaluate their potential cellular perturbations and explore the relationships between their biocompatibility and surface chemistry, we synthesized polymer grafted Fe@CNPs with diverse chemistry modifications on surface and investigated their dynamic cellular responses, cell uptake, oxidative stress and their effects on cell apoptosis and cell cycle. The results show that biocompatibility of Fe@CNPs is both surface chemistry dependent and cell type specific. Except for the carboxyl modified Fe@CNPs, all other Fe@CNPs present low toxicity and can be used for further functionalization and in a wide range of biomedical applications.
nanomaterials; core/shell nanoparticles; biocompatibility; RT-CES; cytotoxicity
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
The development and optimization of near-infrared (nIR) absorbing nanoparticles for use as photothermal cancer therapeutic agents has been ongoing. We have previously reported on larger layered gold / silica nanoshells (~140 nm) for combined therapy and imaging applications. This work exploits the properties of smaller gold / gold sulfide (GGS) nIR absorbing nanoparticles (~35–55 nm) that provide higher absorption (98% absorption & 2% scattering for GGS versus 70% absorption & 30% scattering for gold/silica nanoshells) as well as potentially better tumor penetration. In this work we demonstrate ability to ablate tumor cells in vitro, and efficacy for photothermal cancer therapy, where in an in vivo model we show significantly increased long-term, tumor-free survival. Further, enhanced circulation and bio-distribution is observed in vivo. This class of nIR absorbing nanoparticles has potential to improve upon photothermal tumor ablation for cancer therapy.
Near Infrared; nanoshells; gold / gold sulfide nanoparticles; photothermal therapy; cancer therapy
Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications.
Multifunctional nanoparticles; magnetic nanoparticles; targeting ligand; bioconjugation; surface engineering; long circulation
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
This paper reviews the recent research progress in syntheses and applications of dumbbell-like nanoparticles. It first describes the general synthesis of dumbbell-like nanoparticles containing noble metal and magnetic NPs/or quantum dots. It then outlines the interesting optical and magnetic properties found in these dumbbell nanoparticles. The review further highlights several exciting application potentials of these nanoparticles in catalysis and biomedicine.
Dumbbell nanoparticles; multifunctional nanoparticles; nanoparticle catalyst; nanomedicine
The optimization of the coated metallic nanoparticles and nanoshells is a current challenge for biological applications, especially for cancer photothermal therapy, considering both the continuous improvement of their fabrication and the increasing requirement of efficiency. The efficiency of the coupling between illumination with such nanostructures for burning purposes depends unevenly on their geometrical parameters (radius, thickness of the shell) and material parameters (permittivities which depend on the illumination wavelength). Through a Monte-Carlo method, we propose a numerical study of such nanodevice, to evaluate tolerances (or uncertainty) on these parameters, given a threshold of efficiency, to facilitate the design of nanoparticles. The results could help to focus on the relevant parameters of the engineering process for which the absorbed energy is the most dependant. The Monte-Carlo method confirms that the best burning efficiency are obtained for hollow nanospheres and exhibit the sensitivity of the absorbed electromagnetic energy as a function of each parameter. The proposed method is general and could be applied in design and development of new embedded coated nanomaterials used in biomedicine applications.
(170.0170) Medical optics and biotechnology; (170.3880) Medical and biological imaging; (290.2200) Extinction
Multifunctional colloidal core-shell nanoparticles of magnetic nanocrystals (of iron oxide or FePt) or gold nanorods encapsulated in silica shells doped with the fluorescent dye, Tris(2,2′-bipyridyl)dichlororuthenium(II) hexahydrate (Rubpy) were synthesized. The as-prepared magnetic nanocrystals are initially hydrophobic and were coated with silica using a microemulsion approach, while the as-prepared gold nanorods are hydrophilic and were coated with silica using a Stöber-type of process. Each approach yielded monodisperse nanoparticles with uniform fluorescent dye-doped silica shells. These colloidal heterostructures have the potential to be used as dual-purpose tags—exhibiting a fluorescent signal that could be combined with either dark-field optical contrast (in the case of the gold nanorods), or enhanced contrast in magnetic resonance images (in the case of magnetic nanocrystal cores). The optical and magnetic properties of the fluorescent silica-coated gold nanorods and magnetic nanocrystals are reported.
Synthetic nanoparticles are emerging as versatile tools in biomedical applications, particularly in the area of biomedical imaging. Nanoparticles 1 – 100 nm in diameter have dimensions comparable to biological functional units. Diverse surface chemistries, unique magnetic properties, tunable absorption and emission properties, and recent advances in the synthesis and engineering of various nanoparticles suggest their potential as probes for early detection of diseases such as cancer. Surface functionalization has expanded further the potential of nanoparticles as probes for molecular imaging.
To summarize emerging research of nanoparticles for biomedical imaging with increased selectivity and reduced nonspecific uptake with increased spatial resolution containing stabilizers conjugated with targeting ligands.
This review summarizes recent technological advances in the synthesis of various nanoparticle probes, and surveys methods to improve the targeting of nanoparticles for their application in biomedical imaging.
Structural design of nanomaterials for biomedical imaging continues to expand and diversify. Synthetic methods have aimed to control the size and surface characteristics of nanoparticles to control distribution, half-life and elimination. Although molecular imaging applications using nanoparticles are advancing into clinical applications, challenges such as storage stability and long-term toxicology should continue to be addressed.
biomedical imaging; molecular imaging; nanoparticle synthesis; surface modification; targeting
Biocompatible silica-overcoated magnetic nanoparticles containing an organic fluorescence dye, rhodamine B isothiocyanate (RITC), within a silica shell [50 nm size, MNP@SiO2(RITC)s] were synthesized. For future application of the MNP@SiO2(RITC)s into diverse areas of research such as drug or gene delivery, bioimaging, and biosensors, detailed information of the cellular uptake process of the nanoparticles is essential. Thus, this study was performed to elucidate the precise mechanism by which the lung cancer cells uptake the magnetic nanoparticles. Lung cells were chosen for this study because inhalation is the most likely route of exposure and lung cancer cells were also found to uptake magnetic nanoparticles rapidly in preliminary experiments. The lung cells were pretreated with different metabolic inhibitors. Our results revealed that low temperature disturbed the uptake of magnetic nanoparticles into the cells. Metabolic inhibitors also prevented the delivery of the materials into cells. Use of TEM clearly demonstrated that uptake of the nanoparticles was mediated through endosomes. Taken together, our results demonstrate that magnetic nanoparticles can be internalized into the cells through an energy-dependent endosomal-lysosomal mechanism.
A549 cells; cellular uptake; endocytosis; magnetic nanoparticle