Ultrasensitive Optical Detection and Elimination of Residual Microtumors with a Postoperative Implantable Hydrogel Sensor for Preventing Cancer Recurrence

In vivo optical imaging of trace biomarkers in residual microtumors holds significant promise for cancer prognosis but poses a formidable challenge. Here, a novel hydrogel sensor is designed for ultrasensitive and specific imaging of the elusive biomarker. This hydrogel sensor seamlessly integrates a molecular beacon nanoprobe with fibroblasts, offering both high tissue retention capability and an impressive signal-to-noise ratio for imaging. Signal amplification is accomplished through exonuclease I-mediated biomarker recycling. The resulting hydrogel sensor sensitively detects the biomarker carcinoembryonic antigen with a detection limit of 1.8 pg mL-1 in test tubes. Moreover, it successfully identifies residual cancer nodules with a median diameter of less than 2 mm in mice bearing partially removed primary triple-negative breast carcinomas (4T1). Notably, this hydrogel sensor is proven effective for the sensitive diagnosis of invasive tumors in post-surgical mice with infiltrating 4T1 cells, leveraging the role of fibroblasts in locally enriching tumor cells. Furthermore, the residual microtumor is rapidly photothermal ablation by polydopamine-based nanoprobe under the guidance of visualization, achieving approximate to 100% suppression of tumor recurrence and lung metastasis. This work offers a promising alternative strategy for visually detecting residual microtumors, potentially enhancing the prognosis of cancer patients following surgical interventions. A postoperative implantable hydrogel sensor integrating a molecular beacon (MB) nanoprobe and fibroblasts is designed for visual detection and elimination of residual microtumors by ultrasensitive in situ monitoring of trace biomarkers, whose amplification of the signal is achieved by fibroblast-mediated local enrichment of tumor cells and spatially selective release of exonuclease I (exo I)-triggered biomarker recycling.image