Human-Body-Temperature Triggerable Phase Transition of W-VO₂@PEG Nanoprobes with Strong and Switchable NIR-II Absorption for Deep and Contrast-Enhanced Photoacoustic Imaging.

Abstract

The immense potential of temperature-responsive nanomaterials for use as contrast agents has propelled much recent research and development in the field of photoacoustic (PA) imaging, while the exorbitant transition temperature exceeding the human-tolerable range and the low reversibility of the reported temperature-sensitive nanosystems are still two severe issues that hinder effective imaging and long-term monitoring in practical applications. Herein, we propose a high-performing thermoresponsive polyethylene glycol-coated tungsten-doped vanadium dioxide (W-VO₂@PEG) nanoprobe (NP) with strong and switchable optical absorption in the near-infrared-II (NIR-II) biowindow (1000-1700 nm) near human-body temperature, to achieve deep and contrast-enhanced PA imaging. Our study shows that the PA signal amplitude of W-VO₂@PEG NPs at 1064 nm increases up to 260% when the temperature increases from 35 °C to 45 °C, with a signal fluctuation of less than 10% after 10 temperature cycles, therefore enabling great potential of "off-to-on" dynamic contrast-enhanced imaging capability in deep-seated tissues. Experiments on tissue-mimicking phantoms and <i>in vitro</i> chicken breast showed that, by levering the prepared W-VO₂@PEG NPs and dynamically modulating the temperature field with an external NIR optical stimulus, contrast-enhanced PA images of the target can be obtained with an imaging depth up to 1.5 cm. Furthermore, <i>in vivo</i> potential of the prepared thermoresponsive NPs for the detection and identification of deep-seated tumors by directly comparing to conventional "always on" NPs has been demonstrated. Our work will offer feasible guidance for the development of smart temperature-activatable PA NPs with improved imaging depth and imaging contrast.