What is new in nanoparticle-based photoacoustic imaging?

Abstract

Photoacoustic imaging combines the high temporal and spatial resolution of ultrasound with the good contrast and spectral tuning of optical imaging. Contrast agents are used in photoacoustic imaging to further increase the contrast and specificity of imaging or to image a specific molecular process, e.g., cell-surface proteins or small molecule biomarkers. Nanoparticle-based contrast agents are important tools in photoacoustic imaging because they offer intense and stable signal and can be targeted to specific molecular processes. In this review, we describe some of the most interesting and recent advances in nanoparticle-based photoacoustic imaging including inorganic nanoparticles, organic/polymeric nanoparticles, nanoparticle coatings, multimodality imaging, as well as emerging topics in the field. WIREs Nanomed Nanobiotechnol 2017, 9:e1404. doi: 10.1002/wnan.1404 For further resources related to this article, please visit the WIREs website.

Fig. 1. Basics of Photoacoustics

A) Ultrasound and photoacoustic imaging both use acoustic data (curved black lines) to create an image. In ultrasound, impedance mismatch creates contrast. In photoacoustics, incident light (red arrow) causes thermal expansion and hence a pressure difference (black lines). B) Contrast agents link biology and medicine via an imaging signal. Nanoparticles make excellent reporters because they have high signal intensity and stability.

Fig. 2. Biodegradable gold nanoparticles

A) Small gold spheres are bound together with a pH sensitive polymer. At endosomal pH values (~5), this polymer releases the small gold spheres. This causes a change in the absorbance spectrum (B). This is important because the larger gold cluster can be used for imaging, and the smaller spheres can then clear from the body via the kidney. Reproduced courtesy of American Chemical Society.

Fig. 3. Imaging Reactive Oxygen Species with Acoustic Data and Semiconducting Nanoparticles

Nanoparticles based on benzothiadiazole groups are responsive to reactive oxygen species and produce more blue-shifted acoustic emission in the presence of reactive oxygen species (+Zymosan; right) than control animals (−Zymosan; left). Ratiometric photoacoustic imaging (700 nm/820 nm) can then be used to monitor expression of these molecules. (Zymosan is a glucan that induces experimental sterile inflammation.) Reproduced courtesy of Nature Publishing Group.

Fig. 4. In vivo Imaging of uranyl cation

A) A porphyrinoid macrocycle produces photoacoustic signal when the uranyl cation is chelated because of increased aromaticity (heavy black line). B) Photoacoustic spectrum for free macrocycle (ligand), uranium-complexed porphyrin (complex), and the complex solubilized in PLGA nanoparticles (Complex-NP). C) TEM of nanoparticles at two different magnifications. The in vivo imaging of 100 µL of 0.38 nM NPs with the uranium complex (D) or empty macrocycle (E) highlights the obvious signal difference. Note the scale and intensity bar in D and E apply to both panels. White dashed circle indicates the injection site. Reproduced with permission from The Royal Society of Chemistry.

Fig. 5. Homotypic Targeting

Nanoparticles can be coated with the cell membrane of lysed cancer cells. This membrane contains the entire repertoire of cell surface markers, which can help direct the nanoparticle to the tumor after injection into the systemic circulation. This is in contrast to traditional targeting approaches that use a single marker of interest, e.g. folate, epidermal growth factor receptor, integrins. Reproduced courtesy of American Chemical Society.

Fig. 6. Strategy for Self-assembling Nanoparticles

In this strategy a small molecule contains an imaging agent (red), an enzymatic target (green), and activatable linkers (orange/yellow). When the enzyme cleaves the protecting group, the system self-cyclizes. This process can repeat to make nanoaggregates containing many copies of the imaging agent at the site of interest. This could potentially increase target accumulation more than systematically delivered nanoparticles.