Production, Characterization, and Application of Hydrophobin‐Based IR780 Nanoparticles for Targeted Photothermal Cancer Therapy and Advanced Near‐Infrared Imaging

Abstract As a promising approach for breast cancer treatment, photothermal therapy (PTT) features high spatial selectivity, noninvasiveness, and minimal drug resistance. IR780 (a near‐infrared fluorescent dye) serves as an effective photosensitizer in PTT cancer therapy. However, the clinical application of IR780 in PTT has been hindered by its poor water solubility and unstable photostability. In this study, a genetically engineered dual‐functional fusion protein tLyP‐1‐MGF6 is successfully constructed and expressed, which presents a novel use of hydrophobin MGF6 for its amphiphilicity combined with the tumor‐penetrating peptide tLyP‐1 to create an innovative carrier for IR780. These results show this fusion protein serving as a biodegradable and biocompatible carrier, significantly improves the water solubility of IR780 when formulated into nanoparticles. These studies demonstrate that the IR780@tLyP‐1‐MGF6 nanoparticles significantly enhance tumor targeting and photothermal therapeutic efficacy in comparison with control in vitro and in vivo. These advancements highlight the potential of the unique combination hydrophobin‐based IR780 delivery system as a multifunctional nanoplatform for integrated imaging and targeted photothermal treatment of breast cancer.