Red blood cell-like-Fe<sub>2</sub>O<sub>3</sub> nanocrystals as contrast agents for PAT on a rat cerebral cortex <italic>in vivo</italic>

Abstract

Photoacoustic tomography (PAT) is a novel, noninvasive, nonionizing and cost-effective imaging modality, which combines the merits of optical and ultrasonic imaging, and has been recently prosperous for biomedical applications. Owing to the high optical absorption of hemoglobin this endogenous molecules contrast agent, PAT has been confirmed to be a mighty imaging tool for blood vessels. With the development of science and technology, nanotechnology has increasingly been brought to the forefront due to the unique physical and chemical properties of nanomaterials, such as small size effect, surface and interface effects. During the past few decades, nanoparticles designed for high photoacoustic contrast agents have become a burgeoning scientific favorite. Iron oxide has been extensively investigated because of good magnetic properties, thermal and chemical stability as well as its low cost, easy and environmentally friendly. Especially, due to its good compatibility and hypotoxicity, it has been widely used in nuclear magnetic resonance imaging (MRI) contrast agents. Besides, many functional groups (cathecol, amine, quinone) of dopamine hydrochloride (DA) can be reacted with a large number of molecules so as to provide a friendly method to make many bio-molecules tightly immobilized on the surface. Red blood cell-like-Fe2O3 nanoparticles modified by DA (DA@Fe2O3) were prepared in order to be utilized as an optical contrast agent in PAT. Red blood cell-like-Fe2O3 nanoparticles were synthesized by a facile hydrothermal synthesis method and modified by dopamine hydrochloride. The cell toxicity of DA@Fe2O3 was surveyed by incubating with NIH3T3 cells using MTT assy. The ex vivo photoacoustic performance of DA@Fe2O3 was tested by using a transparent tube containing only suspensions with a range of concentrations and mixed with blood by PAT system. DA@Fe2O3 as contrast agent in photoacoustic tomography of a rat cerebral cortex was also observed. DA@Fe2O3 has not shown any significant cell growth inhibition at concentrations ranging from 3.125 to 200 μ g/mL. PA contrast enhancement properties in vitro of DA@Fe2O3 got more remarkable with the concentration of nanoparticles increasing. The contrast of PAT images of the cerebral cortex of a rat after DA@Fe2O3 aqueous suspension at a specific concentration injection through the tail was enhanced. DA@Fe2O3 shows hypotoxicity and good biological compatibility. DA@Fe2O3 presents a strong absorption to the specific wavelength laser and excellent PA contrast enhancement properties in vitro and in vivo . These results demonstrated that DA@Fe2O3 could be utilized as innovative, commercially viable, promising candidates as alternative optical contrast agents.