The possible combination of specific physicochemical properties operating at unique sites of action within cells and tissues has led to considerable uncertainty surrounding nanomaterial toxic potential. We have investigated the importance of proteins adsorbed onto the surface of two distinct classes of nanomaterials (single-walled carbon nanotubes [SWCNTs]; 10-nm amorphous silica) in guiding nanomaterial uptake or toxicity in the RAW 264.7 macrophage-like model. Albumin was identified as the major fetal bovine or human serum/plasma protein adsorbed onto SWCNTs, while a distinct protein adsorption profile was observed when plasma from the Nagase analbuminemic rat was used. Damaged or structurally altered albumin is rapidly cleared from systemic circulation by scavenger receptors. We observed that SWCNTs inhibited the induction of cyclooxygenase-2 (Cox-2) by lipopolysaccharide (LPS; 1 ng/ml, 6 h) and this anti-inflammatory response was inhibited by fucoidan (scavenger receptor antagonist). Fucoidan also reduced the uptake of fluorescent SWCNTs (Alexa647). Precoating SWCNTs with a nonionic surfactant (Pluronic F127) inhibited albumin adsorption and anti-inflammatory properties. Albumin-coated SWCNTs reduced LPS-mediated Cox-2 induction under serum-free conditions. SWCNTs did not reduce binding of LPS(Alexa488) to RAW 264.7 cells. The profile of proteins adsorbed onto amorphous silica particles (50-1000 nm) was qualitatively different, relative to SWCNTs, and precoating amorphous silica with Pluronic F127 dramatically reduced the adsorption of serum proteins and toxicity. Collectively, these observations suggest an important role for adsorbed proteins in modulating the uptake and toxicity of SWCNTs and nano-sized amorphous silica.

Water-in-oil (w/o) microemulsion synthesis of 70 nm size monodisperse TAT (a cell penetrating peptide, CPP) conjugated, FITC (fluorescein isothiocyanate) doped silica nanoparticles (TAT-FSNPs) is reported; human lung adenocarcinoma (A549) cells (in vitro) and rat brain tissue (in vivo) were successfully labeled using TAT-FSNPs.

Fluorescent, radio‐opaque, and paramagnetic silica nanoparticles 100 ± 10 nm in size are developed by incorporating fluorescent tris(2,2′‐bipyridyl) dichlororuthenium(II) hexahydrate and paramagnetic gadolinium ions. The nanoparticles are radio‐opaque due to the presence of electron‐dense Ru and Gd atoms. It is estimated that each nanoparticle carries about 16 000 Gd3+ ions. The multimodality of the silica nanoparticles is shown by fluorescence (Figure, left) and X‐ray (right) imaging.

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Optical imaging technique has strong potential for sensitive cancer diagnosis, particularly at the early stage of cancer development. This is a sensitive, non-invasive, non-ionizing (clinically safe) and relatively inexpensive technique. Cancer imaging with optical technique however greatly relies upon the use of sensitive and stable optical probes. Unlike the traditional organic fluorescent probes, fluorescent nanoparticle probes such as dye-doped nanoparticles and quantum dots (Qdots) are bright and photostable. Fluorescent nanoparticle probes are shown to be very effective for sensitive cancer imaging with greater success in the cellular level. However, cancer imaging in an in vivo setup has been recently realized. There are several challenges in developing fluorescent nanoparticle probes for in vivo cancer imaging applications. In this review, we will discuss various aspects of nanoparticle design, synthesis, surface functionalization for bioconjugation and cancer cell targeting. A brief overview of in vivo cancer imaging with Qdots will also be presented. Importance of Diagnostic Cancer ImagingAccording to the American Cancer Society's annual report (1), about 570,280 people are expected to die of various cancers in the year 2005 in the United States of America (USA). Early cancer diagnosis, in combination with the precise cancer therapies could eventually save millions of lives. The diagnosis of cancer at the early stage is extremely challenging and has been an active research area these days. Existing diagnostic non-invasive imaging techniques such as Computed Tomography (CT), Magnetic Resonance (MR), Positron Emission Tomography (PET), Single Photon emission CT (SPECT), and Ultrasound (US) are suitable for the diagnosis of abnormalities in the macroscopic level. However, sensitive imaging of abnormalities in the microscopic level has been very challenging. Substantial research efforts are being made for the development of better cancer imaging techniques in the microscopic level. Several imaging techniques such as, SPECT, PET, and optical techniques have shown great promises (2, 3) in the microscopic level. Using fluorescent nanoparticle probes, the feasibility of developing optical imaging technique for the sensitive detection of cancer has been recently demonstrated (4, 5). Nanoparticle Probes for Cancer Tissue ImagingLike normal tissues, cancer tissues can interact with light photons by absorption, scattering, and reflection. It is, therefore, expected that the optical image would be somewhat distorted. Again, most tissues autofluoresce (6) upon interaction with the light in the UV and visible spectrum. To develop a robust optical imaging system it is thus important to address all sorts of light interaction with tissue as well as tissue autofluorescence. Again, effective loading of nanoparticle probes to cancer target is important prior to imaging. Firstly, nanoparticles with the excitation and emission band maxima in the near-infrared (NIR) range (650 nm to 900 nm) are highly preferable for deep tiss...

We describe a novel technique of using fluorescent silica nanoparticles (FSNPs) to detect over-expressed folate receptors, as typical for certain malignancies (metastatic adenocarcinoma, pituitary adenoma and others). Using Stöber's method with some modification, 135 nm size FSNPs were synthesized by a hydrolysis and co-condensation reaction of tetraethylorthosilicate (TEOS), fluorescein labeled (3-aminopropyl)triethoxysilane (APTS) and a water-dispersible silane reagent, (3-trihydroxysilyl)propyl methylphosphonate (THPMP) in the presence of ammonium hydroxide catalyst. Folic acid (folate) was covalently attached to the amine modified FSNPs by a carbodiimide coupling reaction. The characterization of folate-FSNPs was performed using a variety of spectroscopic (UV-VIS and fluorescence), microscopic (transmission electron microscopy, TEM) and light scattering techniques. Folate conjugated FSNPs were then targeted to human squamous cancer cells (SCC-9). Laser scanning confocal images successfully demonstrated the labeling of SCC-9 cells and the efficacy of FSNP based detection system.

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The sections in this article are Introduction Cancer Imaging Techniques Computed Tomography ( CT ) Scanning Magnetic Resonance ( MR ) Positron Emission Tomography ( PET ) Single‐photon Emission CT ( SPECT ) Ultrasonography ( US ) Optical Imaging Basics of Optical Imaging Optical Imaging Techniques Optical Contrast Agents Nanoparticles for Optical Imaging Why Nanoparticles for Optical Imaging? Development of Nanoparticle‐based Contrast Agents Quantum Dots Gold Nanoparticles Dye‐doped Silica Nanoparticles Optical Imaging of Cancer with Nanoparticles Active Targeting Passive Targeting Cancer Imaging with Quantum Dots Cancer Imaging with Gold Nanoparticles Cancer Imaging with Dye‐doped Silica Nanoparticles Other Nanoparticle‐based Optical Contrast Agents Conclusions and Perspectives Acknowledgments