Hypoxia-activated and improved cell uptake near-infrared fluorescent probe for precise guiding surgical resection

Abstract

Tumor imaging and fluorescence-guided surgical resection offers a promising therapeutic approach for the treatment of cancer with simple operation. Hypoxia, as a crucial feature in solid tumor, is closely related to the design of hypoxia-activated fluorescent probes to distinguish tumor and normal tissue. In present, many hypoxia-activated fluorescent probes have received widespread attention in various imaging applications. However, as far as we know, hypoxia-activated near-infrared fluorescent probe for tumor fluorescence-guided surgical resection is not currently reported. Therefore, a hypoxia-activated near-infrared fluorescent probes Fu-Cy was synthesized. It was able to produce near-infrared fluorescence (780 nm) in specific response to overexpressed nitroreductase in hypoxic tumors with rapid response. However, the uptake of the probe in the cell will affect the imaging ability of the probe. Therefore, acetazolamide (AZ), a well-known inhibitor of carbonic anhydrase IX (CAIX), was coupled to Fu-Cy by clicking reaction to obtain the improved probe Az-Fu-Cy, which is more absorbed by cancer cells than Fu-Cy. Thus, Az-Fu-Cy can effectively distinguish between tumors and normal organs by spraying. Interestingly, it showed accurate guidance during surgical resection.