Rapid, Non‐Invasive, Accurate Diagnosis and Efficient Clearance of Metastatic Lymph Nodes

Abstract Sentinel lymph node (SLN) biopsy is currently the standard procedure for clinical cancer diagnosis and treatment, but still faces the risks of false negatives and tumor metastasis, as well as time‐consuming pathological evaluation procedure. Herein, we proposed a near‐infrared‐II (NIR‐II, 1000–1700 nm) theranostic nanosystem (FLAGC) for rapid, non‐invasive, accurate diagnosis and efficient clearance of metastatic lymph nodes in breast cancer. Initialized by chlorin e6 (Ce6), a pH‐sensitive amphiphilic amino acid fluorenylmethoxycarbonyl‐L‐histidine (Fmoc‐His) was assembled with Gd 3+ , luminol, and AgAuSe quantum dots (AAS QDs) to form FLAGC. In FLAGC, luminol and AAS QDs form a NIR‐II chemical resonance energy transfer (CRET) system (Luminol‐AAS); Ce6 initiates the assembly and also serves as a photosensitizer. Upon subcutaneous injection, FLAGC is easily drained into SLNs, achieving their precise localization. Subsequently, the acidity of tumor microenvironment triggers the rapid disassembly of FLAGC, exposing Luminol‐AAS. myeloperoxidase (MPO) secreted by tumor‐associated macrophages and neutrophils in SLNs mediates the oxidation of luminol, lighting up AAS QDs through the CRET process for precise diagnosis of metastatic lymph nodes. Moreover, highly efficient clearance of positive lymph nodes is achieved through Ce6‐mediated photodynamic therapy. Our strategy provides a new paradigm for identifying and eliminating clinically metastatic lymph nodes.