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

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 surface-enhanced Raman scattering (SERS) nanoplatform is proposed for ultra-sensitively monitoring the substance related with oxidative stress (hydrogen sulfide, H2S), 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 Ag2S by H2S 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 H2S to promote the production of reactive oxygen species, and the depletion of reactive sulfur species (GSH and H2S) 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.

A multi-channel responsive AuNP@COF core-shell nanoprobe for simultaneous subcellular profiling of multiple cancer biomarkers.

The abnormal change in the expression profile of multiple cancer biomarkers is closely related to tumor progression and therapeutic effect. Due to their low abundance in living cells and the limitations of existing imaging techniques, simultaneous imaging of multiple cancer biomarkers has remained a significant challenge. Here, we proposed a multi-modal imaging strategy to detect the correlated expression of multiple cancer biomarkers, MUC1, microRNA-21 (miRNA-21) and reactive oxygen (ROS) in living cells, based on a porous covalent organic framework (COF) wrapped gold nanoparticles (AuNPs) core-shell nanoprobe. The nanoprobe is functionalized with Cy5-labeled MUC1 aptamer, a ROS-responsive molecule (2-MHQ), and a miRNA-21-response hairpin DNA tagged by FITC as the reporters for different biomarkers. The target-specific recognition can induce the orthogonal molecular change of these reporters, producing fluorescence and Raman signals for imaging the expression profiles of membrane MUC1 (red fluorescence channel), intracellular miRNA-21 (green fluorescence channel), and intracellular ROS (SERS channel). We further demonstrate the capability of the cooperative expression of these biomarkers, along with the activation of NF-κB pathway. Our research provides a robust platform for imaging multiple cancer biomarkers, with broad potential applications in cancer clinical diagnosis and drug discovery.