Synthesis And Application Of Gold Nanorods For In Vivo Photoacoustic Imaging

The photoacoustic tomography imaging(PAI)technology combines advantages of acoustic imaging and pure optical imaging.PAI can achieve high penetration depth and better image quality to provide the images of internal bleeding,thrombus diseases biological tissue abnormalities and tumor cells under human skin cover nondestructively,it is significant for early detection of cancer judgment and can win a best time to for the treatment.How to improve the response of photoacoustic signal strength is the root problem to enhance the quality images and is also the hot spot in PAI researches.Rod-shaped nanomaterials equipped with tunable longitudinal surface plasma resonance absorption peaks,so they are the most potential PAI agents.Among them,the gold nanorod has stable chemical properties deciding it is very suitab le for applying to organisms.What's more the gold nanorods have higher absorption intens ity at the longitudinal resonance absorption peak,which decides the gold nanorods are widely used in PAI as contrast agents.Based on the understanding of photoacoustic signals' generation mechanism,biological tissue's absorption properties,we used gold nanorods in PAI enhanc ing s ignal response and conducted the following research:(1)Subsize gold nanorods(7.1±0.5 nm in diameter,18±1.0 nm in length)were synthesized by a simple step hydrothermal and surface modificated by thiol-PEG,which made the biocompatibility increased by 115%(the experiment concentration was 1 nM).The modified gold nanorods(1 nM)was balance mixed with fresh pure cow blood and collected photoacoustic signals.The photoacoustic signal intensity was increased by 180%.The mouse was injected with thiol-PEG modified gold nanorods by tail vein and imaged in PAI system.Reconstructed image of the mouse cerebral blood vessels was in high resolution and basically restored anatomical structures in mouse brain cortex.(2)Tunable-aspect-ratio gold nanorods was synthesized by practice three-step cycle hydrothermal.The aspect ratio was controlled in range of 8.5~16 by adjusting ascorbic acid(AA)in reaction process,and the longitudinal plasma resonance absorption peak was shifted between 680 and 1100 nm accordingly.Gold nanorods equipped with typical absorption peak(Au TR)were modified by thiol-PEG and tested the biocompatibility as a representative.The modified Au TR's relative cell viability rate reached 92% and was fully fit for organisms.PAI and signals were collected in vitro by two kinds gold nanorods,and the photoacoustic signal's response linear increase with the increase of solution concentration: when the concentration of gold nanorods was 1 nM,photoacoustic signal strength of Au TR(at 800 nM)increased 5.7 times,with the same condition of Rod1(680 nM)increased 5.5 times.Au TR-PEG was injected in mouse and imaged at different time points.As is illustrated in reconstructed images,photoacoustic signal got strongest at 25 min,then signal intens ity attenuation and in line with no-injection at 2h.When the laser excitation wavelength was 800 nm,reconstruction image of Au TR-PEG injection group's signal-to-noise ratio is 3.1 times to the blank control group.And when the laser excitation wavelength was 680 nm,image's signal-to-noise ratio of Au Rod1-PEG injection group is 3.9 times to the blank control group.(3)Gold nanorods possessed with broad absorption band range from 680 nm to 1100 nm or even further was synthesized by hydrothermal method.The biocompatibility of gold nanorods were increased 2.5 times through thiol-PEG(the concentration was 1 nM).The PEG modified gold nanorods was balance mixed with fresh pure blood and imaged in vitro under two group lasers,which the wavelength was 532 nm/800 nm/900 nm and 532 nm/680 nm/828 nm.According to the quality of reconstruction images,the mouse was injected with PEG modified gold nanorods and imaged under 532 nm/680 nm/828 nm.And the reconstruction images of mouse brain vascular were high quality at all three wavelength lasers.The reconstruction images of gold nanorods injection group respectively under 680 nm and 828 nm lasers were operated and obtained the brain blood oxygen saturation distribution in mice.