A Tumor‐Activatable Liposomal Nanoprobe for Selective Visualization of Metastatic Lymph Nodes

The precise identification of sentinel lymph nodes (SLNs) during surgery and assessment of their benign status is crucial for accurate tumor staging and optimal treatment strategizing. Currently, a deficiency exists in non-invasive in vivo diagnostic techniques that can accurately pinpoint SLNs during surgery while simultaneously evaluating their benign status. Here, a tumor-activatable liposomal nanoprobe (nTAL) is developed, remotely loaded with clinically approved photosensitizer, methyl aminolevulinate (MAL), to noninvasively visualize the tumor metastasis lymph nodes (LNs) with precision. Benefited from the highly efficient LNs draining of nanosized liposome and tumor cell-specific transformation of the non-fluorescent MAL to fluorescent protoporphyrin IX (PPIX), nTAL succeeded in targeting the SLNs and differentiated the metastatic from the benign ones with a positive correlation between PPIX generation and tumor cell infiltration in LNs. Moreover, the nTAL technology is capable of probing the early metastatic stage with a primary tumor size of 50 mm³. This study provides a new strategy for intraoperative visualization of real-time sentinel node dissection.