A Hybrid Protein-Oxygen Nanomedicine Overcomes Osimertinib Resistance in NSCLC via HIF-1α/VEGF/EGFR Inhibition

作者：Guanming Jiang, Xuyi Liu, Dou Zhang, Zhenying Diao, Xiaojun Yang, Qinquan Tan, Shiyuan Chen, Wan Zhang, Xiumao Yin, Ting Yin, Xiaozhen Wang, Jianping Zhou · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s531571 · 被引用次数：4 · 研究领域：Nanoplatforms for cancer theranostics、Cancer, Hypoxia, and Metabolism、Nanoparticle-Based Drug Delivery

Purpose: Osimertinib, established as the frontline treatment for advanced non-small cell lung cancer (NSCLC), can effectively prolong progression-free survival. However, it faces the problem of reduced treatment persistence due to acquired drug resistance. Meanwhile, tumor hypoxia is also a key driver of drug resistance. This study proposes a hybrid protein oxygen nanocarrier combined with osimertinib and ginsenoside Rg3 to address the drug resistance issue of NSCLC through multiple mechanisms. Methods: A hybrid protein-oxygen multifunctional nanoplatform (OG@HPO) was engineered by co-encapsulating OSI and GRg3 within oxygen-rich protein matrices. Initial confirmed the synthesis of OG@HPO and characterized its drug/oxygen release. Subsequent in vitro assays verified OG@HPO's tumoricidal activity and elucidated its mechanistic. Finally, in vivo evaluations validated the nanoplatform's tumor targeting and anticancer efficacy. Results: Preliminary experiments confirmed successful OG@HPO preparation and validated its drug/oxygen release capacities. In vitro assays demonstrated the potent cytotoxic effects of OG@HPO against H1975 OR cells. In vivo biodistribution studies revealed excellent tumor-targeting of OG@HPO in H1975 OR xenograft mice. Subsequent 18 days therapeutic monitoring showed superior antitumor efficacy accompanied and favorable biosafety profile of OG@HPO. More importantly, in vitro and in vivo studies demonstrated that OG@HPO effectively oxygenate tumor microenvir...