Prostate Stem Cell Antigen-Targeted DNA Aptamer Probe with Ultrahigh Tumor Contrast for Precision Fluorescence-Guided Surgery of Prostate Cancer.

Fluorescence-guided surgery (FGS) offers a potential strategy to improve complete tumor resection in prostate cancer (PCa); however, clinical application has been limited by an insufficient tumor-to-background ratio (TBR) of available probes. Here, we report the development of GGA-sNIR, a near-infrared (NIR) fluorescent probe engineered by conjugating a high-affinity DNA aptamer specific for a prostate stem cell antigen (PSCA) with a monocarboxy indocyanine green (ICG) derivative. The conjugate adopts a stable three-dimensional structure that not only enables precise target recognition but also protects against nuclease degradation, markedly enhancing its in vivo stability. GGA-sNIR exhibits nanomolar binding affinity ( = 54.91 nM) and is specifically internalized by PSCA-positive cells. In subcutaneous tumor models, the probe achieved a peak TBR of 26 and showed prolonged tumor retention exceeding 48 h. Crucially, in an orthotopic PCa model, GGA-sNIR allowed real-time, high-contrast visualization of tumor margins during laparoscopic surgery, facilitating precise and complete resection. Further validation using ex vivo human lymph node specimens confirmed its ability to selectively detect PSCA-positive metastases. With its ultrahigh contrast, demonstrated efficacy in intraoperative guidance, and strong translational potential, GGA-sNIR represents a promising molecular tool for advancing precision surgery in prostate cancer.