Advanced contrast nanoagents for photoacoustic molecular imaging, cytometry, blood test and photothermal theranostics

Abstract

Various nanoparticles have raised significant interest over the past decades for their unique physical and optical properties and biological utilities. Here we summarize the vast applications of advanced nanoparticles with a focus on carbon nanotube (CNT)-based or CNT-catalyzed contrast agents for photoacoustic (PA) imaging, cytometry and theranostics applications based on the photothermal (PT) effect. We briefly review the safety and potential toxicity of the PA/PT contrast nanoagents, while showing how the physical properties as well as multiple biological coatings change their toxicity profiles and contrasts. We provide general guidelines needed for the validation of a new molecular imaging agent in living subjects, and exemplify these guidelines with single-walled CNTs targeted to αvβ3, an integrin associated with tumor angiogenesis, and golden carbon nanotubes targeted to LYVE-1, endothelial lymphatic receptors. An extensive review of the potential applications of advanced contrast agents is provided, including imaging of static targets such as tumor angiogenesis receptors, in vivo cytometry of dynamic targets such as circulating tumor cells and nanoparticles in blood, lymph, bones and plants, methods to enhance the PA and PT effects with transient and stationary bubble conjugates, PT/PA Raman imaging and multispectral histology. Finally, theranostic applications are reviewed, including the nanophotothermolysis of individual tumor cells and bacteria with clustered nanoparticles, nanothrombolysis of blood clots, detection and purging metastasis in sentinel lymph nodes, spectral hole burning and multiplex therapy with ultrasharp rainbow nanoparticles.

Photoacoustic flow cytometry

“…For D ≈ d ≈ 10 μm, in vessels with diameters of 50 μm, 2 mm (e.g., hand vein), and 1 cm (e.g., carotid artery) having different velocities pulse rates will be f ≥ 500 Hz, 2 kHz, and 50 kHz, respectively. To improve signal-to-noise ratios (SNRs) by averaging PA signals from each exposed cell without temporal overlapping of thermal effects, f can be increased until f ≤ 1/τ T , where τ T = D 2 /28 k is the thermal relaxation time (for a spherical target with diameter of D ), and k the thermal diffusion [39]. For D = 10 μm and k = 1.4 × 10 −7 m 2 /s (for water), f ≤ 25 kHz.…”

“…11A). Indeed, intravenous injection of carbon nanotubes (CNTs) led to the appearance of PA signal traces from the mouse tibia [39]. To exclude possible PA background signals from CNTs circulating in blood vessels between fiber used for delivery laser radiation and bones, the fiber was gently attached to the skin in an area with no visible vessels.…”

Photoacoustic brain imaging: from microscopic to macroscopic scales

“…However, nanoparticles can be more easily engineered for PA molecular imaging; in particular, the peak absorption wavelength can be easily tuned [78, 79, 92, 93]. Numerous nanoparticles with various sizes, shapes, and compositions have been used for photoacoustic molecular imaging, especially in vascular enhancement [94, 95], early cancer detection [96-98], drug delivery [99, 100] and sentinel lymph node mapping [101, 102].…”

A bifunctional curcumin analogue for two-photon imaging and inhibiting crosslinking of amyloid beta in Alzheimer's disease

“…They could also have similar interaction mechanisms and specificity requirements for the target. In traditional approaches, imaging probes and drugs are pursued separately, which are time-consuming and costly 3, 4 . To overcome this disadvantage, developing agents that have potentials for therapy and imaging (theranostic) is highly desirable.…”