Hypoxia, Oxygen delivery nanoparticles, Immunotherapy, Granzyme B, Positron emission tomography imaging, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5

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.