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<p>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 CaCO<sub>3</sub>@quercetin-Mn nanoparticles (CQM NPs) integrating dual-stage macrophage reprogramming with <i>T</i><sub>1</sub>-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&#xa0;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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月14日

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  • Meiju Sui,
  • Kairu Xie,
  • Yingying Luo,
  • Haiqiang Wang,
  • Hao Sheng,
  • Sen Yue,
  • Xiaoxun Liu,
  • Sha Li,
  • Jung Soo Suk,
  • Shizhen Chen,
  • Daiqin Chen,
  • Xin Zhou

摘要

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.

Graphical abstract