Programmable macrophage-polarizing nanoparticles for MRI-guided early detection and treatment of pulmonary metastases

Metastatic lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the urgent need for early detection and intervention strategies. Current diagnostic and therapeutic methods often fall short in sensitivity and efficacy, particularly for early-stage disease. In this study, we develop CaCO₃@quercetin-Mn nanoparticles (CQM NPs) integrating dual-stage macrophage reprogramming with T₁-weighted magnetic resonance imaging (MRI) enhancement for theranostic management of pulmonary metastasis. CQM NPs exploit dynamic macrophage polarization: initial M2 polarization promotes nanoparticles accumulation in metastatic lesions, enabling detection of lesions as small as 0.11 mm, while subsequent acid/glutathione (GSH)-triggered degradation reprograms tumor-associated macrophages to antitumor M1 phenotype, suppressing metastatic growth by 81.64% and preventing circulating tumor cells (CTCs) from colonizing the lungs by 78.08%. These findings demonstrate a significant improvement in MRI sensitivity and an integrated approach to therapy, contrasting with traditional methods that separate these challenges. This "detect-to-treat" paradigm bridges the critical gap between imaging sensitivity and immunomodulatory therapy, offering a blueprint for precision nanomedicine in metastatic cancers.