Tumor Microenvironment‐Activated NIR‐II Nanotheranostic System for Precise Diagnosis and Treatment of Peritoneal Metastasis

Abstract Activatable theranostic systems show potential for improved tumor diagnosis and therapy owing to high detection specificities, effective ablation, and minimal side‐effects. Herein, a tumor microenvironment (TME)‐activated NIR‐II nanotheranostic system (FEAD1) for precise diagnosis and treatment of peritoneal metastases is presented. FEAD1 was fabricated by self‐assembling the peptide Fmoc‐His, mercaptopropionic‐functionalized Ag 2 S quantum dots (MPA‐Ag 2 S QDs), the chemodrug doxorubicin (DOX), and NIR absorber A1094 into nanoparticles. We show that in healthy tissue, FEAD1 exists in an NIR‐II fluorescence “off” state, because of Ag 2 S QDs‐A1094 interactions, while DOX remains in stealth mode. Upon delivery of FEAD1 to the tumor, the acidic TME triggers its disassembly through breakage of the Fmoc‐His metal coordination and DOX hydrophobic interactions. Release of A1094 switches on Ag 2 S fluorescence, illuminating the tumor, accompanied by burst release of DOX within the tumor tissue, thereby achieving precise tumor theranostics. This TME‐activated theranostic strategy holds great promise for future clinical applications.