Self-Assembly of Precisely Fluorinated Albumin for Dual Imaging-Guided Synergistic Chemo–Photothermal–Photodynamic Cancer Therapy
Lijun Zhu, Haijun Yu, Mou Jiang, Changsheng Ke, Hanxiong Long, Maosong Qiu, Lei Zhang, Chaohui Ye, Xin Zhou, Zhong‐Xing Jiang, Shizhen Chen
Abstract
Although albumin has been extensively used in nanomedicine, it is still challenging to fluorinate albumin into fluorine-19 magnetic resonance imaging ( 19 F MRI)-traceable theranostics because existing strategies lead to severe 19 F signal splitting, line broadening, and low 19 F MRI sensitivity. To this end, 34-cysteine-selectively fluorinated bovine serum albumins (BSAs) with a sharp singlet 19 F peak have been developed as 19 F MRI-sensitive and self-assembled frameworks for cancer theranostics. It was found that fluorinated albumin with a non-binding fluorocarbon and a long linker is crucial for avoiding 19 F signal splitting and line broadening. With the fluorinated BSAs, paclitaxel (PTX) and IR-780 were self-assembled into stable, monodisperse, and multifunctional nanoparticles in a framework-promoted self-emulsion way. The high tumor accumulation, efficient cancer cell uptake, and laser-triggered PTX sharp release of the BSA nanoparticles enabled 19 F MRI-near infrared fluorescence imaging (NIR FLI)-guided synergistic chemotherapy (Chemo), photothermal and photodynamic therapy of xenograft MCF-7 cancer with a high therapeutical index in mice. This study developed a rational synthesis of 19 F MRI-sensitive albumin and a framework-promoted self-emulsion of multifunctional BSA nanoparticles, which would promote the development of protein-based high-performance biomaterials for imaging, diagnosis, therapy, and beyond.