Label free and real time detection of nonfluorescent drugs inside living cells has been realized by using surface-enhanced Raman scattering (SERS). For the first time, the characteristics of 6-mercapotopurine and methimazole, two different drugs, were monitored simultaneously by SERS in living cells. Particularly, the processes of diffusion and metabolism of drugs occurring in the intracellular matrix were investigated. The results indicate that the metabolism speed of 6-mercapotopurine in living HeLa cells is much faster than that of methimazole. Moreover, the detection sensitivity of intracellular drugs has also been checked and a low detection limit of 1 nM was obtained of drug 6-mercapotopurine in a single HeLa cell.
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