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, we present a novel hydrogel sensor 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 detected the biomarker carcinoembryonic antigen with a detection limit of 1.8 pg/mL in test tubes. Moreover, it successfully identified 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 was 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 nearly 100% suppression of tumor recurrence and lung metastasis. Our work offers a promising alternative strategy for visually detecting residual microtumors, potentially enhancing the prognosis of cancer patients following surgical interventions. This article is protected by copyright. All rights reserved.