Integrated pipeline for ultrasensitive protein detection in cancer nanomedicine

Although nanotechnologies have attractive attributes in cancer therapy, their full potential has yet to be realized due to challenges in their translation to clinical settings. The evaluation of cancer nanomedicine efficacy in preclinical in vivo studies is limited to tumor size and animal survival metrics, which do not provide adequate understanding of the nanomedicine's mechanism of action. To address this, we have developed an integrated pipeline called nanoSimoa that combines an ultrasensitive protein detection technique (Simoa) with cancer nanomedicine. As a proof-of concept, we assessed the therapeutic efficacy of an ultrasound-responsive mesoporous silica nanoparticle (MSN) drug delivery system on OVCAR-3 ovarian cancer cells using CCK-8 assays to evaluate cell viability and Simoa assays to measure IL-6 protein levels. The results demonstrated significant reductions in both IL-6 levels and cell viability following nanomedicine treatment. In addition, a Ras Simoa assay (limit of detection: 0.12 pM) was developed to detect and quantify Ras protein levels in OVCAR-3 cells, which are undetectable by commercial enzyme-linked immunosorbent assays (ELISA). These results suggest that nanoSimoa has the potential to guide the development of cancer nanomedicines and predict their behavior in vivo, making it a valuable tool for preclinical testing and accelerating the development of precision medicine if its generalizability is confirmed.