Smart Nanoplatform for Visualizing Hydrogen Sulfide and Amplifying Oxidative Stress to Tumor Apoptosis

Abstract

Oxidative stress is involved in various signaling pathways and serves a key role in inducing cell apoptosis. Therefore, it is significant to monitor oxidative stress upon drug release for the assessment of therapeutic effects in cancer cells. Herein, a glutathione (GSH)-responsive surfaceenhanced Raman scattering (SERS) nanoplatform is proposed for ultrasensitively monitoring the substance related with oxidative stress (hydrogen sulfide, H 2 S), depleting reactive sulfur species and releasing anticancer drugs to amplify oxidative stress for tumor apoptosis. The Au@Raman reporter@Ag (Au@M@Ag) nanoparticles, where a 4-mercaptobenzonitrile molecule as a Raman reporter was embedded between layers of gold and silver to obtain sensitive SERS response, were coated with a covalent organic framework (COF) shell to form a core−shell structure (Au@M@Ag@COFs) as the SERS nanoplatform. The COF shell loading doxorubicin (DOX) of Au@M@ Ag@COFs exhibited the GSH-responsive degradation capacity to release DOX, and its Ag layer as the sensing agent was oxidized to Ag 2 S by H 2 S to result in its prominent changes in SERS signals with a low detection limit of 0.33 nM. Moreover, the releasing DOX can inhibit the generation of H 2 S to promote the production of reactive oxygen species, and the depletion of reactive sulfur species (GSH and H 2 S) in cancer cells can further enhance the oxidative stress to induce tumor apoptosis. Overall, the SERS strategy could provide a powerful tool to monitor the dynamic changes of oxidative stress during therapeutic processes in a tumor microenvironment.