Reversibly Photoswitching Upconversion Nanoparticles for Super‐Sensitive Photoacoustic Molecular Imaging

• Published in: Angewandte Chemie International Edition Vol. 61; no. 19; pp. e202116802 - n/a
• Main Authors: Liu, Cheng, Zheng, Xianchuang, Dai, Tingting, Wang, Huiliang, Chen, Xian, Chen, Bing, Sun, Tianying, Wang, Feng, Chu, Steven, Rao, Jianghong
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 02.05.2022
• Edition: International ed. in English
• Subjects: Acoustics; Animals; Background noise; Contrast agents; Contrast media; Hemoglobin; Humans; Imaging; Imaging Agents; Mice; Molecular Imaging - methods; Nanocrystals; Nanoparticles; Nanoparticles - chemistry; Near-infrared; Penetration depth; Photoacoustic Imaging; Photoacoustic Techniques - methods; Pigments; Reversible Photoswitching; Sensitivity; Spatial discrimination; Spatial resolution; Spectrum Analysis; Upconversion; Upconversion Nanoparticles; Reversible Photoswitching; Near-infrared; Imaging Agents; Photoacoustic Imaging; Upconversion Nanoparticles
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202116802

Photoacoustic (PA) imaging uses light excitation to generate the acoustic signal for detection and improves tissue penetration depth and spatial resolution in the clinically relevant depth of living subjects. However, strong background signals from blood and pigments have significantly compromised the sensitivity of PA imaging with exogenous contrast agents. Here we report a nanoparticle‐based probe design that uses light to reversibly modulate the PA emission to enable photoacoustic photoswitching imaging (PAPSI) in living mice. Such a nanoprobe is built with upconverting nanocrystals and photoswitchable small molecules and can be switched on by NIR light through upconversion to UV energy. Reversibly photoswitching of the nanoprobe reliably removed strong tissue background, increased the contrast‐to‐noise ratio, and thus improved imaging sensitivity. We have shown that PAPSI can image 0.05 nM of the nanoprobe in hemoglobin solutions and 104 labeled cancer cells after implantation in living mice using a commercial PA imager. An upconverting nanoparticle probe can be switched on and off by near‐infrared (NIR) light for multiple cycles of photoacoustic imaging (PA). Through reversible modulation of the probe PA activation state, a background‐free PA signal can be recovered in imaging 0.05 nM of the probe in hemoglobin (Hb) solution and 104 labeled cancer cells subcutaneously implanted in mice.