Zhu Lijun, Li Yu, Jiang Mou, Ke Changsheng, Long Hanxiong, Qiu Maosong, Zhang Lei, Ye Chaohui, Zhou Xin, Jiang Zhong-Xing, Chen Shizhen
School of Pharmaceutical Sciences, Wuhan University, Wuhan430071, China.
Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan430071, China.
ACS Appl Mater Interfaces. 2023 Jan 18;15(2):2665-2678. doi: 10.1021/acsami.2c19161. Epub 2023 Jan 5.
Although albumin has been extensively used in nanomedicine, it is still challenging to fluorinate albumin into fluorine-19 magnetic resonance imaging (F MRI)-traceable theranostics because existing strategies lead to severe F signal splitting, line broadening, and low F MRI sensitivity. To this end, 34-cysteine-selectively fluorinated bovine serum albumins (BSAs) with a sharp singlet F peak have been developed as 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 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 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 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.
尽管白蛋白已在纳米医学中广泛应用，但将白蛋白氟化以用于氟-19磁共振成像（F MRI）可追踪的诊疗仍具有挑战性，因为现有策略会导致严重的F信号分裂、谱线展宽以及较低的F MRI灵敏度。为此，已开发出具有尖锐单重态F峰的34-半胱氨酸选择性氟化牛血清白蛋白（BSA），作为用于癌症诊疗的F MRI敏感且自组装的框架。研究发现，带有非结合性氟碳和长连接基的氟化白蛋白对于避免F信号分裂和谱线展宽至关重要。利用氟化的BSA，紫杉醇（PTX）和IR-780以框架促进的自乳化方式自组装成稳定、单分散且多功能的纳米颗粒。BSA纳米颗粒的高肿瘤蓄积、高效癌细胞摄取以及激光触发的PTX快速释放，能够在小鼠体内以高治疗指数实现F MRI-近红外荧光成像（NIR FLI）引导的协同化疗（Chemo）、光热和光动力治疗异种移植的MCF-7癌症。本研究开发了一种合理合成F MRI敏感白蛋白以及框架促进的多功能BSA纳米颗粒自乳化的方法，这将推动基于蛋白质的高性能生物材料在成像、诊断、治疗及其他领域的发展。
