Wang Xingyi, Fang Hanyi, Hu Wenzhu, Feng Yuan, Zhou Zhangyongxue, Hu Mengyan, Jiang Dawei, Zhang Yongxue, Lan Xiaoli
Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Hubei Province Key Laboratory of Molecular Imaging, 1277 Jiefang Avenue, Wuhan, 430022, China.
J Nanobiotechnology. 2025 Mar 7;23(1):186. doi: 10.1186/s12951-025-03257-6.
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.
有限的治疗反应和不完善的监测方法是成功进行免疫治疗面临的严峻挑战。在缺氧的肿瘤微环境中招募和激活免疫细胞是逆转免疫抑制和提高免疫治疗效果的关键。在本研究中，我们设计了仿生输氧纳米颗粒（CmPF），用于在肿瘤环境中进行同源靶向和缓解缺氧。CmPF靶向肿瘤微环境并输送氧气以减轻缺氧，从而促进肿瘤部位的免疫细胞活性。此外，采用靶向颗粒酶B的正电子发射断层扫描（PET）成像来监测体内免疫细胞活性因免疫治疗效果而发生的变化。CmPF与卡铂和PD-1抑制剂联合使用可显著抑制肿瘤生长达2.4倍，显示出CmPF增强免疫治疗效果的潜力。免疫组织化学进一步证实关键免疫标志物的表达增加，突出了肿瘤微环境的重编程。本研究表明，缓解缺氧可提高肿瘤免疫治疗效果，并引入了一种非侵入性PET成像方法用于动态、实时评估治疗反应。
