Multiwavelength Photoacoustic Imaging and Plasmon Resonance Coupling of Gold Nanoparticles for Selective Detection of Cancer

Abstract

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...

Characterisation of gold nanoparticles synthesised by leaf and seed extract ofSyzygium cuminiL.

“…Among various synthesis methods, plant-mediated synthesis is preferred due to its cost effectiveness and environment-friendly nature [3,4]. GNP have applications in therapeutic [5], catalysis [2], immunoassay and immunosensing [6], diagnostic and drug delivery [7][8][9][10], analyte sensing [11][12][13], cancer cell diagnostics and selective photothermal therapy [14,15], photoacoustic imaging [16,17] and cancer treatment [18]. Various plant extracts have been explored for the synthesis of GNP, namely tamarind [19], Aloe vera [20], Pelargonium graveolens [21], Diopyros kaki [22], Eucalyptus camaldulensis and Pelargonium roseum [23], coriander [24], Scutellaria barbata [25], lemongrass [26], Datura metel, Carica papaya and Solanum melongena [27].…”

Photoacousic Molecular Imaging of Inflammatory Disease

“…Excess PAA in solution was removed by brief centrifugation and GNRs were dispersed in 10 ml of PBS followed by the addition of 1.25 ml of 1M N-ethyl-N-3-dimethylamino propyl-carbodiimide (EDC) (Sigma-Aldrich, St. Louis, MO, USA) and 1.25 ml of 1M N-hydroxy-succinimide (NHS) (Sigma-Aldrich, St. Louis, MO, USA). [10][11][12][13][14]16] After 20 min, the reaction mixture was added to 20 µl of FITC labeled anti-ICAM-1 antibody or PE labeled anti-E-selectin antibody. The EDC/NHS mixture forms an active ester intermediate with the -COOH groups of PAA which undergoes amidation reaction with the -NH2 group in the FITC labeled anti-ICAM-1 and PE labeled anti-E-selectin antibodies to yield the GNR-antibody conjugates.…”

Analog Front-End Circuitry in Piezoelectric and Microphone Detection of Photoacoustic Signals

“…Piezoelectric transducers are used mainly in photoacoustics of liquids [19][20][21][22] and solids for which the forms allow for direct contact with the transducer [23][24][25][26]-e.g., semiconductor structures [25,26]. They are also commonly used in medical and imaging applications [27,28], as well as for the study of nanoparticle suspensions [29,30]. Microphones are applied mainly in photoacoustic investigations of gases [1,2,[31][32][33][34] and such solids in which piezoelectric detection would be difficult-e.g., powders [35,36].…”