Silver nanoparticles (AgNPs) play significant roles in various cancer cells such as functional heterogeneity, microenvironmental differences, and reversible changes in cell properties (e.g., chemotherapy). There is a lack of targets for processes involved in tumor cellular heterogeneity, such as metabolic clampdown, cytotoxicity, and genotoxicity, which hinders microenvironmental biology. Proteogenomics and chemical metabolomics are important tools that can be used to study proteins/genes and metabolites in cells, respectively. Chemical metabolomics have many advantages over genomics, transcriptomics, and proteomics in anticancer therapy. However, recent studies with AgNPs have revealed considerable genomic and proteomic changes, particularly in genes involved in tumor suppression, apoptosis, and oxidative stress. Metabolites interact biochemically with energy storage, neurotransmitters, and antioxidant defense systems. Mechanobiological studies of AgNPs in cancer metabolomics suggest that AgNPs may be promising tools that can be exploited to develop more robust and effective adaptive anticancer therapies. Herein, we present a proof-of-concept review for AgNPs-based proteogenomics and chemical metabolomics from various tumor cells with the help of several technologies, suggesting their promising use as drug carriers for cancer therapy.

The dynamic regulation of signal transduction at plasma membrane microdomains remains poorly understood due to limitations in current experimental approaches. Genetically encoded biosensors based on fluorescent resonance energy transfer (FRET) can provide high spatiotemporal resolution for imaging cell signaling networks. Here, distinctive regulation of focal adhesion kinase (FAK) and Ca 2+ signals are visualized at different membrane microdomains by FRET using membrane‐targeting biosensors. It is shown that rigidity‐dependent FAK and Ca 2+ signals in human mesenchymal stem cells (hMSCs) are selectively activated at detergent‐resistant membrane (DRM or rafts) microdomains during the cell–matrix adhesion process, with minimal activities at non‐DRM domains. The rigidity‐dependent Ca 2+ signal at the DRM microdomains is downregulated by either FAK inhibition or lipid raft disruption, suggesting that FAK and lipid raft integrity mediate the in situ Ca 2+ activation. It is further revealed that transient receptor potential subfamily M7 (TRPM7) participates in the mobilization of Ca 2+ signals within DRM regions. Thus, the findings provide insights into the underlying mechanisms that regulate Ca 2+ and FAK signals in hMSCs under different mechanical microenvironments.