In vivo fluorescence bioimaging of ascorbic acid in mice: Development of an efficient probe consisting of phthalocyanine, TEMPO, and albumin

After a groundbreaking study demonstrated that a high dose of ascorbic acid selectively kills cancer cells, the compound has been tested in the clinic against various forms of cancers, with some success. However, in vivo tracing of intravenously injected ascorbic acid has not been achieved. Herein, we successfully imaged ascorbic acid intravenously injected into mice based on the discovery of a novel, highly sensitive, and appropriately selective fluorescent probe consisting of silicon phthalocyanine (SiPc) and two 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radicals, i.e., R2c. The radicals in this R2c were encapsulated in dimeric bovine serum albumin, and the sensitivity was >100-fold higher than those of other R2c-based probes. Ascorbic acid intravenously injected into mice was efficiently transported to the liver, heart, lung, and cholecyst. The present results provide opportunities to advance the use of ascorbic acid as cancer therapy.