Label-Free Surface-Enhanced Raman Scattering Imaging to Monitor the Metabolism of Antitumor Drug 6-Mercaptopurine in Living Cells

Abstract

The molecular processes of drugs from cellular uptake to intracellular distribution as well as the intracellular interaction with the target molecule are critically important for the development of new antitumor drugs. In this work, we have successfully developed a label-free surface-enhanced Raman scattering (SERS) technique to monitor and visualize the metabolism of antitumor drug 6-mercaptopurine in living cells. It has been clearly demonstrated that Au@Ag NPs exhibit an excellent Raman enhancement effect to both 6-mercaptopurine and its metabolic product 6-mercaptopurine-ribose. Their different ways to absorb at the surface of Au@Ag NPs lead to the obvious spectral difference for distinguishing the antitumor drug and its metabolite by SERS spectra. The Au@Ag NPs can easily pass through cell membranes in a large amount and sensitively respond to the biological conversion of 6-mercaptopurine in tumor cells. The Raman imaging can visualize the real-time distribution of 6-mercaptopurine and its biotransformation with the concentrations in tumor cells. The SERS-based method reported here is simple and efficient for the assessments of drug efficacy and the understanding of the molecular therapeutic mechanism of antitumor drugs at the cellular level.

Quantum cytosensor for early detection of cancer

“…The peak at 1,059 cm −1 is assigned to phenylalanine and 1,178 cm −1 is assigned to tyrosine (Han et al, ; Huefner et al, ). Protein denaturation occurs in cells as a response to external stress.…”

Raman Imaging Spectroscopy: History, Fundamentals and Current Scenario of the Technique

“…Studies on spatial changes and with the time of cytochemistry in colonies of human embryonic steam cells were performed by Konorov et al 72 This allowed a better understanding of the niches of these colonies and aspects of the tissue, morphologies and organ trajectories. Han et al 73 studied the metabolism of antitumor drug 6-mercaptopurine in living cells. Using SERS, the authors could visualize the real-time distribuition of drug and its biotransformation in tumor cells.…”

Bioanalytical applications of surface-enhanced Raman spectroscopy: de novo molecular identification

“…131 They monitored the real-time metabolism of 6-mercaptopurine in living tumor cells. It was reported that the 6MP and the 6MPR absorbed to the NP surface through the thiol group and the lone pair on the N atom.…”

“…The dominate vibrational bands were associated with the purine ring therefore there was significant spectral overlap between the different analytes. 131 Aqueous silver colloids have also been used to detect other low level anticancer drugs such as sunitinib, SN-38, irinotecan, paclitaxel, and doxorubicin at 633 nm excitation. 132 The colloids and analyte mixtures were drop coated onto aluminum.…”