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 (H₂ O₂ ) 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.

Keywords: combined radiochemotherapy; holo-lactoferrin; hypoxia microenvironment; liposomes; photoacoustic imaging.