Holo‐Lactoferrin Modified Liposome for Relieving Tumor Hypoxia and Enhancing Radiochemotherapy of Cancer

Abstract Hypoxic microenvironments in the solid tumor play a negative role in radiotherapy. Holo‐lactoferrin (holo‐Lf) is a natural protein, which acts as a potential ligand of transferrin receptor (TfR). In this work, an anticancer drug, doxorubicin (Dox)‐loaded liposome‐holo‐Lf nanocomposites, is developed for tumor targeting and imaging guided combined radiochemotherapy. Dox‐loaded liposome‐holo‐Lf (Lf‐Liposome‐Dox) nanocomposites exhibit significant cellular uptake likely owing to the TfR receptor‐mediated targeting accumulation of Lf‐Liposome‐Dox nanocomposites. Additionally, the nanocomposites exhibit high accumulation in the tumor site after intravenous injection as evidenced from in vivo fluorescence imaging. More importantly, it is found that the holo‐Lf has the ability to catalyze the conversion of hydrogen peroxide (H 2 O 2 ) to oxygen for relieving the tumor hypoxic microenvironment. Photoacoustic imaging further confirms the abundant generation of oxygen in the presence of Lf‐Liposome‐Dox nanocomposites. Based on these findings, in vivo combined radiochemotherapy is performed using Lf‐Liposome‐Dox as therapeutic agent, achieving excellent cancer treatment effect. The study further promotes the potential biomedical application of holo‐Lf in cancer treatment.