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  3. Oxygen-delivery nanoparticles enhanced immunotherapy efficacy monitored by granzyme B PET imaging in malignant tumors

Oxygen-delivery nanoparticles enhanced immunotherapy efficacy monitored by granzyme B PET imaging in malignant tumors

  • J Nanobiotechnology. 2025 Mar 7;23(1):186. doi: 10.1186/s12951-025-03257-6.
Xingyi Wang # 1 2 3,  Hanyi Fang # 4 5 6,  Wenzhu Hu 1 2 3,  Yuan Feng 1 2 3,  Zhangyongxue Zhou 1 2 3,  Mengyan Hu 1 2 3,  Dawei Jiang 1 2 3,  Yongxue Zhang 1 2 3,  Xiaoli Lan 7 8 9
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Hubei Province Key Laboratory of Molecular Imaging, 1277 Jiefang Avenue, Wuhan, 430022, China.
  • 3 Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China.
  • 4 Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. fanghanyi@hust.edu.cn.
  • 5 Hubei Province Key Laboratory of Molecular Imaging, 1277 Jiefang Avenue, Wuhan, 430022, China. fanghanyi@hust.edu.cn.
  • 6 Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China. fanghanyi@hust.edu.cn.
  • 7 Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xiaoli_lan@hust.edu.cn.
  • 8 Hubei Province Key Laboratory of Molecular Imaging, 1277 Jiefang Avenue, Wuhan, 430022, China. xiaoli_lan@hust.edu.cn.
  • 9 Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Wuhan, 430022, China. xiaoli_lan@hust.edu.cn.
  • # Contributed equally.
PMID: 40050894 DOI: 10.1186/s12951-025-03257-6
Abstract

Limited treatment response and inadequate monitoring methods stand firmly before successful immunotherapy. Recruiting and activating immune cells in the hypoxic tumor microenvironment is the key to reversing immune suppression and improving immunotherapy efficacy. In this study, biomimetic oxygen-delivering nanoparticles (CmPF) are engineered for homologous targeting and hypoxia alleviation within the tumor environment. CmPF targets the tumor microenvironment and delivers oxygen to reduce hypoxia, thereby promoting immune cell activity at the tumor site. In addition, granzyme B-targeted positron emission tomography (PET) imaging is employed to monitor immune cell activity changes in response to immunotherapy efficacy in vivo. The combination of CmPF with carboplatin and PD-1 inhibitors significantly suppresses tumor growth by 2.4-fold, exhibiting the potential of CmPF to enhance the efficacy of immunotherapy. Immunohistochemistry further confirms increased expression of key immune markers, highlighting the reprogramming of the tumor microenvironment. This study demonstrates that hypoxia alleviation enhances tumor immunotherapy efficacy and introduces a non-invasive PET imaging method for dynamic, real-time assessment of therapeutic response.

Keywords

Granzyme B; Hypoxia; Immunotherapy; Oxygen delivery nanoparticles; Positron emission tomography imaging.

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