A-D-A-D-A Structured Organic Semiconductor Liposomes for NIR-II Fluorescence Imaging and Surgical Navigation of Lymph Node Metastasis

Abstract

Fluorescence-guided surgery enables precise intraoperative "mapping" of malignant tissue, allowing surgeons to identify and excise small or occult lesions while maximally preserving healthy tissues, thereby reducing the risk of recurrence and metastasis and promoting postoperative recovery. However, clinically approved fluorescent contrast agents functioning in the second near-infrared (NIR-II) window are scarce. In this study, we report an n-type small-molecule organic semiconductor dye (BTP-IC-OD) with an acceptor-donor-acceptor-donor-acceptor (A-D-A-D-A) backbone, incorporated into folate receptor-targeted NIR-II fluorescent liposomal nanoparticles (FA-LNP@BTP-IC-OD) for high-contrast imaging and real-time surgical navigation of lymph node metastases. Using the deep-tissue penetration and high spatiotemporal resolution of NIR-II fluorescence emission, FA-LNP@BTP-IC-OD enables non-invasive and high-sensitivity detection of metastatic lymph nodes in vivo. Furthermore, the bright and stable NIR-II fluorescence emmision signal provides excellent intraoperative visualization, facilitating accurate, real-time fluorescence-guided resection of metastatic lymph nodes in preclinical models. This study highlights the potential of rationally engineered organic semiconductor liposomes as a powerful theranostic nanoplatform that integrates sensitive NIR-II fluorescence imaging diagnostics with improved surgical outcomes for the management of lymph node metastasis.