Self-Enhanced Acoustic Impedance Difference Strategy for Detecting the Acidic Tumor Microenvironment

B-mode ultrasound imaging is a significant anatomic technique in clinic, which can display the anatomic variation in tissues. However, it is difficult to evaluate the functional state of organs and display the physiological information in organisms such as the tumor acidic microenvironment (TME). Herein, inspired by the phenomenon of sonographic acoustic shadow during detecting calculus in clinic, a strategy of self-enhanced acoustic impedance difference is proposed to monitor the acidic TME. BiF3@PDA@PEG (BPP) nanoparticles can self-aggregate in a specific response to the acidic TME to form huge stones BiF3@PDA, resulting in an increase of local tumor density, and further causing a significant acoustic impedance difference. In in vitro experiments, the enhanced ultrasound signals change from 15.2 to 196.4 dB, which can discriminate different pH values from 7.0 to 5.0, and the sensitivity can reach to 0.2 value. In in vivo experiments, the enhanced ultrasound signal is 107.7 dB after BPP self-aggregated, displaying the weak acidic TME that has a close relationship with the size and species of the tumor. More importantly, the accuracy is away from the interference of pressure because huge stones BiF3@PDA change little. However, SonoVue microbubbles will diffuse and rupture under pressure, which results in false positive signals. To sum up, this strategy will be helpful to the further development of ultrasound molecular imaging.

Automated summary

B-mode ultrasound imaging is an important technique for anatomical imaging in clinic, but lacks the ability to evaluate organ function and display physiological information. This study proposes a strategy based on self-enhanced acoustic impedance difference to monitor acidic tumor microenvironment. The results show that this method can effectively discriminate different pH regions and is not affected by pressure interference.