Abnormal cellular biothiol levels are related to many abnormal physiological processes, including cancer, multidrug resistance and Alzheimer's disease, etc. In this study, the nano-aggregates of the background-free surface-enhanced Raman scattering (SERS) tags were constructed and developed for the intracellular biothiol detection via a target-triggered disaggregation process. The plasmonic nano-tags were prepared by coating gold nanoparticles with a Raman reporter (4-mercaptobenzonitrile, MBN), which exhibits a single strong peak in the cellular Raman silent region (1800-2800 cm-1) that can eliminate the background interference of cells. Interestingly, this reporter is also the host ligand for guest mercury ions. The coordination of mercury/cyano group induce the formation of the pre-aggregates of nano-tags and the formed nano-aggregates allowing strong SERS signals of reporters. Intracellular biothiols show higher affinity to mercury ions than the SERS tags do, which can break the hot spot geometry and redisperse tags by taking away mercury ions from nano-aggregates, which dramatically decreases the SERS signals of reporters previously laid on gold nanoparticles. The developed SERS "turn off" method was used for biothiol detections in normal, cancer, drug-resistant cells, and biothiol dynamics during chemotherapy. The results demonstrate that the drug-resistant cells (MCF-ADR) lie in a higher biothiol level than cancer cells (MCF-7 and HepG2), and the normal cells (LO2) give a lower biothiol concentration compared with cancer cells. Moreover, most cancer cells are more sensitive to doxorubicin compared with the normal ones. This study provides an important strategy in learning the cellular processes that are highly associated with intracellular biothiol level.
Keywords: Biothiol; Hot spot; Nanoparticle dispersion; SERS.
Copyright © 2019 Elsevier B.V. All rights reserved.