2. Academic Validation
  3. HIFU postoperative hypoxia-activated metal-organic frameworks modulate the tumor microenvironment to augment immunotherapy

HIFU postoperative hypoxia-activated metal-organic frameworks modulate the tumor microenvironment to augment immunotherapy

  • J Nanobiotechnology. 2026 Feb 1;24(1):200. doi: 10.1186/s12951-026-04079-w.
Chengyan Luo # 1 2,  Dezhou Wu # 1 2,  Song Peng 1,  Siyi Xu 1 2,  Dengke Zhang 1 2,  Xinchang Huang 1 2,  Weiji Qin 1 2,  Hongyan Li 1 2,  Huanan Li 3 4
Affiliations

Affiliations

  • 1 Department of Radiology, Women and Children's Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.
  • 2 State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, P. R. China.
  • 3 Department of Radiology, Women and Children's Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China. [email protected].
  • 4 State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, 400016, P. R. China. [email protected].
  • # Contributed equally.
PMID: 41622222 DOI: 10.1186/s12951-026-04079-w
Abstract

Limited intensity and duration of high-intensity focused ultrasound (HIFU)-induced immune response largely hinder postoperative immunotherapy due to low immunogenicity and immunosuppression of tumor microenvironment (TME). In this study, effect-specific metal-organic frameworks (MOFs) were designed based on the severe hypoxia of postoperative tumors through regulating TME to enhance body's antitumor immune response. The combination of iron ions, hypoxic-activated prodrug banoxantrone, and indoleamine 2,3-dioxygenase (IDO) signaling pathway inhibitor NLG919 is utilized to construct MOFs loaded with CaCO3, which achieves intraoperative monitoring via photoacoustic imaging for precise ablation of tumors. Ingeniously, banoxantrone, within the severely hypoxic environment of tumors induced by HIFU, is activated in the manner of converting enemies into friends and cooperates with iron ions to effectively trigger immunogenic cell death (ICD) in tumors. In addition, the immunosuppressive microenvironment exacerbated by postoperative hypoxia is degraded via the cooperation of NLG919, which blocks the IDO-1 signaling pathway and CaCO3, which consumes lactic acid. Based on these improvements, well-designed MOFs effectively inhibit bilateral tumor growth/metastasis and offer a successful paradigm for improving the overall prognosis of HIFU.

Keywords

Antitumor immune response; HIFU; Hypoxia-activated; Immune microenvironment; Metal-organic frameworks.

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