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

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 in vitro 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, in vivo 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.