AsianScientist (Feb. 1, 2018) – In a study published in Scientific Reports, a team of researchers at the University of Tokyo, Japan, have tracked the levels of vitamin C in live mice using a molecule called R2c.
Vitamin C is best known as a nutrient. In high enough doses, however, vitamin C also shows potential against many cancers, according to recent studies. To successfully develop vitamin C as a medication, it is crucial to probe its concentration in the body, thus ensuring safe and effective doses.
Monitoring the changing levels of a delivered drug is not easy. For vitamin C, one method is to use the reaction between the compound and fluorescent probe molecules, allowing chemists to visually trace its movement through the body. Fluorescence requires light, however, and existing probes use light of the wrong wavelength to penetrate living tissue.
In the present study, a research group led by Dr. Takanori Yokoi of the the University of Tokyo’s Institute of Industrial Science developed a new probe that could be used to illuminate vitamin C in biological tissue. The team designed this probe, called R2c, to react with vitamin C molecules in the body.
“We created R2c from a silicon compound, SiPc, bonded to free radicals. The radicals stop SiPc molecules from aggregating, which would switch off their fluorescence. In turn, each probe molecule is encapsulated in a protein called BSA,” explained Yokoi.
By blocking reactions with chemicals other than the target, BSA ensures that the probe is also selective. R2c reacts rapidly with vitamin C, becoming a fluorescent molecule while remaining sternly aloof to other biological compounds. The team found that hydrogen peroxide, which occurs in the body, could be added to R2c without interfering with the vitamin C signal. This raises the hope that R2c could faithfully pick out vitamin C in human patients as well.
An hour after R2c was injected into the tails of mice, their bodies became fluorescent, highlighting that vitamin C is naturally present in the mice. Next, the mice were injected with an extra dose of vitamin C, raising the concentration above normal. Within ten minutes, the fluorescence signal flared up in the abdomen. This demonstrated that vitamin C immediately accumulates in the abdomen after being administered intravenously.
Like before, the probe signal then spread throughout the body over the next hour. According to the researchers, this is the first time that vitamin C has been directly imaged in a living animal model. Moreover, the probe is highly sensitive, detecting vitamin C down to micromolar amounts. This makes the probe suitable for detecting vitamin C in human blood.
“Our probe is the first to trace vitamin C with sensitivity, speed and selectiveness, and with low toxicity,” said corresponding author Professor Kazuyuki Ishii of the University of Tokyo. “Excitingly, we could watch exactly which organs the vitamin C accumulated in. For clinical cancer treatment, this is invaluable in ensuring that drugs are delivered to the right parts of the body.”
The article can be found at: Yokoi et al. (2017) In vivo Fluorescence Bioimaging of Ascorbic Acid in Mice: Development of an Efficient Probe Consisting of Phthalocyanine, TEMPO, and Albumin.
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Source: University of Tokyo; Photo: Kazuyuki Ishii.
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