Self-assembled nanosphere-cooperated mRNA discriminator for electrochemical analysis of breast cancer metastasis

Metastatic breast cancer exhibits specific characteristics closely associated with mRNA expression profiles. Consequently, sensitive detection of specific mRNAs may facilitate the early warning and identification of breast cancer metastasis at the molecular level, significantly improving patient prognosis. Herein, we present a new electrochemical mRNA discriminator as a tool for analyzing breast cancer metastasis. Specifically, we prepare self-assembled nanospheres that are coated with hyaluronic acid and loaded with duplex-specific nucleases (DSNs) and electrochemically tagged DNA probes targeting two breast cancer metastasis-related mRNAs. By recognizing CD44—an antigen highly expressed on the surface of breast cancer cells—the nanospheres effectively deliver the DNA probes and DSNs into target cells. Thereafter, intracellular target mRNAs hybridize with their corresponding DNA probes, initiating DSN-driven target recycling and releasing a large number of relevant electrochemical molecules. Finally, through host-guest interaction-based enrichment, this discriminator allows for detecting two target mRNAs down to 0.170 pM and 0.127 pM, respectively. Meanwhile, this self-assembled nanosphere-cooperated discriminator enables effective discrimination between highly metastatic and low-metastatic breast cancer cells and exhibits good utility in mouse tumor tissue samples. Therefore, this work may offer an effective tool for detecting breast cancer metastasis-related mRNAs, which is expected to provide insights into analyzing breast cancer metastasis.