Anti‐HER2 scFv‐nCytc‐Modified Lipid‐Encapsulated Oxygen Nanobubbles Prepared with Bulk Nanobubble Water for Inducing Apoptosis and Improving Photodynamic Therapy

Abstract Bulk nanobubbles fascinate scientists because of their stability over long periods of time and their ability to carry gases, leading to numerous potential applications. Considering the hypoxic tumor microenvironment and the advantages of bulk nanobubbles, lipid‐encapsulated oxygen nanobubbles are prepared from free bulk oxygen nanobubbles in this study. The obtained carrier is then modified with a protein fused with the single‐chain antibody of human epidermal growth factor receptor 2 (anti‐HER2 scFv) and tandem‐repeat cytochrome c (anti‐HER2 scFv‐nCytc) to enhance tumor targeting and induce tumor apoptosis. Copper phthalocyanine is used as the photosensitizer to demonstrate how the oxygen in the nanobubbles affects the efficiency of photodynamic therapy (PDT). The combination of anti‐HER2 scFv‐nCytc and PDT synergistically improves the therapeutic effect and alleviates hypoxia in tumors in vivo while causing little inflammatory response. Based on the findings, bulk nanobubble water shows promise in the targeted delivery of oxygen and can be combined with antibody therapy to enhance the efficiency of PDT.