Tumor-derived exosomes play a vital role in the process of cancer development. Quantitative analysis of exosomes and exosome-shuttled proteins would be of immense value in understanding cancer progression and generating reliable predictive biomarkers for cancer diagnosis and treatment. Recent studies have indicated the critical role of exosomal programmed death ligand 1 (PD-L1) in immune checkpoint therapy and its application as a patient stratification biomarker in cancer immunotherapy. Here, we present a nanoplasmonic exosome immunoassay utilizing gold−silver (Au@Ag) core−shell nanobipyramids and gold nanorods, which form sandwich immune complexes with target exosomes. The immunoassay generates a distinct plasmonic signal pattern unique to exosomes with specific exosomal PD-L1 expression, allowing rapid, highly sensitive exosome detection and accurate identification of PD-L1 exosome subtypes in a single assay. The developed nanoplasmonic sandwich immunoassay provides a novel and viable approach for tumor cell-derived exosome detection and analysis with quantitative molecular details of key exosomal proteins, manifesting its great potential as a transformative diagnostic tool for early cancer detection, prognosis, and post-treatment monitoring.

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Disulfiram (DSF) is a thiocarbamate based drug that has been approved for treating alcoholism for over 60 years. Preclinical studies have shown that DSF has anticancer efficacy, and its supplementation with copper (CuII) significantly potentiates the efficacy of DSF. However, the results of clinical trials have not yielded promising results. The elucidation of the anticancer mechanisms of DSF/Cu (II) will be beneficial in repurposing DSF as a new treatment for certain types of cancer. DSF’s anticancer mechanism is primarily due to its generating reactive oxygen species, inhibiting aldehyde dehydrogenase (ALDH) activity inhibition, and decreasing the levels of transcriptional proteins. DSF also shows inhibitory effects in cancer cell proliferation, the self-renewal of cancer stem cells (CSCs), angiogenesis, drug resistance, and suppresses cancer cell metastasis. This review also discusses current drug delivery strategies for DSF alone diethyldithocarbamate (DDC), Cu (II) and DSF/Cu (II), and the efficacious component Diethyldithiocarbamate–copper complex (CuET).

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Therapeutic strategies for ARID1A-mutant ovarian cancers are limited. Higher basal reactive oxygen species (ROS) and lower basal glutathione (GSH) empower the aggressive proliferation ability and strong metastatic property of OCCCs, indicated by the increased marker of epithelial-mesenchymal transition (EMT) and serving the immunosuppressive microenvironment. However, the aberrant redox homeostasis also empowers the sensitivity of DQ-Lipo/Cu in a mutant cell line. DQ, a carbamodithioic acid derivative, generates dithiocarbamate (DDC) in response to ROS, and the chelation of Cu and DDC further generates ROS and provides a ROS cascade. Besides, quinone methide (QM) released by DQ targets the vulnerability of GSH; this effect, plus the increase of ROS, destroys the redox homeostasis and causes cancer cell death. Also importantly, the formed Cu(DDC)2 is a potent cytotoxic anti-cancer drug that successfully induces immunogenic cell death (ICD). The synergistic effect of EMT regulation and ICD will contribute to managing cancer metastasis and possible drug resistance. In summary, our DQ-Lipo/Cu shows promising inhibitory effects in cancer proliferation, EMT markers, and “heat” the immune response.