In Situ imaging of orthotopic kidney cancer in the murine model using an aminopeptidase N activatable fluorescent probe

Abstract

Surgical treatment is the most effective treatment for renal cancer. It is urgent to develop highly selective and sensitive analytical methods for specially lighting up the kidney tumor, so as to achieve accurate imaging-guided surgical resection of cancer tissue. However, the main challenge in real-time and in situ fluorescence imaging of kidney tumor rest with the design of fluorescent probes that not only show renal metabolic pathway to enrich in the kidney cancer cells but also have high activatable signal towards kidney tumor-associated biomarkers. Since aminopeptidase N (APN) acted as a kidney cancer-specific biomarker, herein, a low MW PEGylation and APN-activatable fluorescent probe (HDAPN-PEG) was constructed for in situ near infrared fluorescence (NIRF) visualizing the orthotopic kidney cancer in living mice. HDAPN-PEG was specially activated by APN with good sensitivity and selectivity. HDAPN-PEG dramatically turned on its NIRF signal in kidney cancer cells but kept silent in kidney normal cells. Because of the high renal enrichment and its cancer biomarker specificity, HDAPN-PEG can light up the kidney cancer for in situ imaging of kidney cancer in living mice. This work thus recommends an activable molecular probe that not only promotes mechanistic investigation on the roles of APN in kidney cancer, but also facilitates in situ detection kidney cancer and fluorescence imaging guided nephron sparing surgery.