Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 143, Issue 18, Pages 7196-7202Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c03004
Keywords
-
Categories
Funding
- National Institutes of Health [R35GM133581]
Ask authors/readers for more resources
Photoacoustic imaging using near infrared I light has limitations due to interference from endogenous biomolecules, prompting the development of NIR-II imaging agents for improved sensitivity. The study introduced APNO-1080 as a NIR-II nitric oxide-responsive probe, demonstrating enhanced sensitivity and deep-tissue imaging capabilities in vitro and in vivo models of cancer.
Photoacoustic (PA) imaging has emerged as a reliable in vivo technique for diverse biomedical applications ranging from disease screening to analyte sensing. Most contemporary PA imaging agents employ NIR-I light (650-900 nm) to generate an ultrasound signal; however, there is significant interference from endogenous biomolecules such as hemoglobin that are PA active in this window. Transitioning to longer excitation wavelengths (i.e., NIR-II) reduces the background and facilitates the detection of low abundance targets (e.g., nitric oxide, NO). In this study, we employed a two-phase tuning approach to develop APNO-1080, a NIR-II NO-responsive probe for deep-tissue PA imaging. First, we performed Hammett and Bronsted analyses to identify a highly reactive and selective aniline-based trigger that reacts with NO via N-nitrosation chemistry. Next, we screened a panel of NIR-II platforms to identify chemical structures that have a low propensity to aggregate since this can diminish the PA signal. In a head-to-head comparison with a NIR-I analogue, APNO-1080 was 17.7-fold more sensitive in an in vitro tissue phantom assay. To evaluate the deep-tissue imaging capabilities of APNO-1080 in vivo, we performed PA imaging in an orthotopic breast cancer model and a heterotopic lung cancer model. Relative to control mice not bearing tumors, the normalized turn-on response was 1.3 +/- 0.12 and 1.65 +/- 0.07, respectively.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available