Gold nanoparticles targeting epidermal growth factor receptor via antibody conjugation undergo molecular specific aggregation when they bind to receptors on cell surfaces, leading to a red shift in their plasmon resonance frequency. Capitalizing on this effect, we demonstrate the efficacy of the molecular specific photoacoustic imaging technique using subcutaneous tumor-mimicking gelatin implants in ex-vivo mouse tissue. The results of our study suggest that highly selective and sensitive detection of cancer cells is possible using multiwavelength photoacoustic imaging and molecular specific gold nanoparticles.The developments in the fields of nanotechnology and molecular biology provide a promising platform for detection of cancer at an asymptomatic stage. Bioconjugated nano contrast agents together with imaging techniques can satisfy the compelling need to reliably detect, diagnose and characterize cancer at an early stage. [1][2][3][4][5][6][7] Recently, gold nanoparticles (Au NPs) have gained popularity as nano-sized contrast agents 2,6,[8][9][10][11][12][13][14] for their well-developed bioconjugation protocols, 11,[15][16][17] biocompatibility 18,19 and ease of tuning the optical properties. [20][21][22] Immunotargeted gold nanoparticles have been used to enhance contrast in optical imaging techniques. 6,9,13,14 However, the penetration depth achievable with high resolution optical imaging techniques is limited to a few millimeters. Optical techniques utilizing incoherent light extend the penetration depth to several centimeters while spatial resolution is severely sacrificed. Therefore, an in vivo imaging technique that is sensitive in detecting Au NPs and capable of imaging deep lying structures is desired. Photoacoustic imaging [23][24][25] is a technique that can provide penetration depth on the order of centimeters if near-infrared (NIR) laser light is used. In the photoacoustic phenomenon, 26 electromagnetic energy in the form of light is absorbed and subsequently an acoustic wave is emitted. Using a wideband ultrasound detector the acoustic waves can be detected and spatially resolved to provide an image of the optical absorption properties of the internal tissue structure. [23][24][25] Gold nanoparticles have been used as contrast agents in photoacoustic imaging because of their unique optical absorption properties. 8,10,[27][28][29][30][31] Using three-dimensional (3D) tissue models, we previously demonstrated that highly selective detection of cancer could be achieved using molecular targeted gold nanoparticles and combined photoacoustic and ultrasound imaging. 8,32 In particular, the contrast in the photoacoustic images was attributed to the epidermal growth factor receptor (EGFR) 33,34 leading to plasmon resonance coupling between adjacent gold particles and a red-shift in their absorbance spectra 6,8,9,14 while the nontargeted or isolated gold nanoparticles have absorbance peak at around 520 nm. 8,35,36 In this paper, we demonstrate the efficacy of multiwavelength photoacoustic imagin...

The ability of 20-50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report ~30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of goldcoated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of ~70 iron oxide primary particles with thin gold coatings display intense NIR (700-850 nm) absorbance with a cross section of ~10 −14 m 2 . Because of the thin gold shells with an average thickness of only 2 nm, the r 2 spin-spin magnetic relaxivity is 219 mM −1 s −1 , an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in deionized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of *Address correspondence to: kpj@che.utexas.edu, FELDMANM@uthscsa.edu. Supporting Information Available: Reproducibility in nanorose size distribution; porosity of dextran in the shells about the iron oxide particle; estimation of number of particles per nanocluster; average optical density spectra in macrophages labeled with nanorose by hyperspectral microscopy; and laser vaporization of macrophages in vitro. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2010 September 22. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript nanoparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy. Keywordsgold; iron oxide; nanocluster; near-infrared; macrophage targeted imaging; MRI; atherosclerosis; cancer Clinical imaging and/or therapy with multifunctional nanoparticles that target specific types of cells has the potential to transform health care in cancer, atherosclerosis, and other diseases. When the nanoparticle diameters are reduced to 20-50 nm, the biological pathways in targeted cells can undergo profound changes. [1][2][3][4][5] Small nanoparticles, the size of small viruses, permeate barriers more rapidly including cell membranes and leaky vasculature in cancers. The efficacy of vaccines may be enhanced with ultrasmall 20 nm nanoparticles that can dif...

Rapid point-of-care (POC) diagnostic devices are needed for field-forward screening of severe acute systemic febrile illnesses. Multiplexed rapid lateral flow diagnostics have the potential to distinguish among multiple pathogens, thereby facilitating diagnosis and improving patient care. Here, we present a platform for multiplexed pathogen detection using multi-colored silver nanoplates. This design requires no external excitation source and permits multiplexed analysis in a single channel, facilitating integration and manufacturing.

Metal nanoparticles with surface plasmon resonance (SPR) in the near-infrared region (NIR) are of great interest for imaging and therapy. Presently, gold nanoparticles with NIR absorbance are typically larger than 50nm, above the threshold size of ~5 nm required for efficient renal clearance. As these nanoparticles are not biodegradable, concerns about long-term toxicity have restricted their translation into the clinic. Here, we address this problem by developing a flexible platform for the kinetically-controlled assembly of sub-5 nm ligand-coated gold particles to produce metal/polymer biodegradable nanoclusters smaller than 100 nm with strong NIR absorbance for multimodal application. A key novel feature of the proposed synthesis is the use of weakly adsorbing biodegradable polymers that allows tight control of nanocluster size and, in addition, results in nanoclusters with unprecedented metal loadings, and thus optical functionality. Over time, the biodegradable polymer stabilizer degrades under physiological conditions that leads to disassembly of the nanoclusters into sub-5nm primary gold particles which are favorable for efficient body clearance. This synthesis of polymer/inorganic nanoclusters combines the imaging contrast and therapeutic capabilities afforded by the NIR-active nanoparticle assembly with the biodegradability of a polymer stabilizer.