Near infrared photoacoustic detection of sentinel lymph nodes with gold nanobeacons

Abstract

Detection of sentinel lymph node (SLN) using photoacoustic imaging is an emerging technique for noninvasive axillary staging of breast cancer. Due to the absence of intrinsic contrast inside the lymph nodes, exogenous contrast agents are used for photoacoustic detection. In this work, we have demonstrated near infrared detection of SLN with gold nanobeacons (GNB) providing the photoacoustic contrast in a rodent model. We found that size dictates the in vivo characteristics of these nanoparticles in SLN imaging. Larger nanobeacons with high pay loads of gold were not as efficient as smaller size nanobeacons with lower pay loads for this purpose. Colloidal GNBs were designed as a nanomedicine platform with "soft" nature that is amenable to bio-elimination, an essential feature for in vivo efficacy and safety. The GNBs were synthesized as lipid-or polymerencapsulated colloidal particles incorporating tiny gold nanoparticles (2-4 nm) in three tunable sizes (90 nm, 150 nm and 290 nm). Smaller GNBs were noted trafficking through the lymphatic system and accumulating more efficiently in the lymph nodes in comparison to the bigger nanoagents. At 20 min, the GNBs reached the SLN and were no longer observed within the draining lymphatic vessel. Within one hour post injection, the contrast ratio of the lymphnodes with the surrounding blood vessels was 9:1. These findings were also supported by analytical measurements of the ex vivo tissue samples. Results indicate that cumulative nanoparticle deposition in lymph nodes is size dependent and that high payloads of gold, although offering greater contrast in vitro, may yield nanoagents with poor intradermal migration and lymphatic transport characteristics.

Functionalized nanomaterials: their use as contrast agents in bioimaging: mono- and multimodal approaches

“…Some of those commonly used for PAT include spherical gold NPs [304, 314 -320] , nanorods [321 -327] , nanostars [328] , nanocages [305, 329 -334] , hollow nanoshells [335] , and composite materials with gold nanoshells: SiO 2 @Au, [306,336,337] Fe 3 O 4 @Au, [314] cobalt@gold NPs, [110] gold-speckled silica [316,320] , and gold nanobeacons [338,339] . The reasons for such an attention to gold nanosystems are many fold: they have tunable size-and shape-dependent plasmonic properties [340,341] , which allow them to absorb and scatter light from the visible to NIR region and make them suitable for image-guided therapy [325, 342 -344] and PTA of tumors [345 -347] .…”

Photoacoustic contrast imaging of biological tissues with nanodiamonds fabricated for high near-infrared absorbance

“…8 PA imaging contrast in tissues and vasculature can be greatly enhanced with exogenous optical contrast agents, such as NIR dyes, gold nanoparticles and carbon nanoparticles. [9][10][11] Compared to NIR dyes, due to the well-established surface modification with biologically relevant entities for the tumortargeting studies and the enhanced permeability and retention (EPR) effect that was used to image subcutaneous tumors, nanomaterials stand out as the most significant class of materials being explored for PA imaging applications. 6,12 Gold-based nanomaterials, in particular gold nanoshells, nanorods and nanocages, are among the most useful optical contrast agents in PA imaging due to their size-and shapedependent plasmonic properties.…”

Echographic detectability of optoacoustic signals from low-concentration PEG-coated gold nanorods

“…[1][2][3] In fact, the penetration depth achievable with high-resolution optical imaging techniques is limited to a few millimeters, while optical techniques using incoherent light extend the penetration depth to several centimeters but severely sacrifice spatial resolution. [4][5][6] Optoacoustic imaging reaches a much more suitable compromise by exploiting the photoacoustic effect, 7 achieving increased penetration depths with respect to pure optical methods and improved tissue differentiation with respect to conventional acoustic techniques.…”

“…3,[13][14][15][16] In most cases gold is the metal of choice, due to its high stability, facile chemistry, and easy bioconjugation, 12,17 as well as its generally benign toxicity profile. 15,[18][19][20][21] Therefore, various types of gold NPs have been experimentally tested as optoacoustic CAs, such as nanospheres, 4 nanoshells, 22 hollow nanospheres, 14 nanobeacons, 3 and nanocages, 23 but the class of NPs most significantly explored for optoacoustic imaging applications is represented by gold nanorods (GNRs), 8,15,[24][25][26][27][28] which are also attracting increasing interest because of their exceptional ability to accumulate in tumors 29 and their potential for simultaneous photothermal therapy. 30,31 Nevertheless, important issues related to the application of GNR-enhanced optoacoustic imaging still hinder its translation into clinical routine.…”