MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry , Fuzhou University , Fuzhou 350116 , China.
Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB) , National Institutes of Health (NIH) , Bethesda , Maryland 20892 , United States.
J Am Chem Soc. 2019 May 22;141(20):8158-8170. doi: 10.1021/jacs.8b13902. Epub 2019 May 10.
In the present study, we report the development of magnetic-plasmonic bilayer vesicles assembled from iron oxide-gold Janus nanoparticles (FeO-Au JNPs) for reactive oxygen species (ROS) enhanced chemotherapy. The amphiphilic FeO-Au JNPs were grafted with poly(ethylene glycol) (PEG) on the Au surface and ROS-generating poly(lipid hydroperoxide) (PLHP) on the FeO surface, respectively, which were then assembled into vesicles containing two closely attached FeO-Au NPs layers in opposite directions. The self-assembly mechanism of the bilayered vesicles was elucidated by performing a series of numerical simulations. The enhanced optical properties of the bilayered vesicles were verified by the calculated results and experimental data. The vesicles exhibited enhanced T relaxivity and photoacoustic properties over single JNPs due to the interparticle magnetic dipole interaction and plasmonic coupling. In particular, the vesicles are pH responsive and disassemble into single JNPs in the acidic tumor environment, activating an intracellular biochemical reaction between the grafted PLHP and released ferrous ions (Fe) from FeO NPs, resulting in highly efficient local ROS generation and increased intracellular oxidative stress. In combination with the release of doxorubicin (DOX), the vesicles combine ROS-mediated cytotoxicity and DOX-induced chemotherapy, leading to greatly improved therapeutic efficacy than monotherapies. High tumor accumulation efficiency and fast vesicle clearance from the body were also confirmed by positron emission tomography (PET) imaging of radioisotope Cu-labeled vesicles.
在本研究中，我们报告了由氧化铁-金（FeO-Au）各向异性纳米粒子组装而成的磁性-等离子体双层囊泡的发展，用于活性氧（ROS）增强化学疗法。两亲性的 FeO-Au JNPs 在 Au 表面接枝聚乙二醇（PEG），在 FeO 表面接枝产生 ROS 的聚脂氢过氧化物（PLHP），然后将其组装成双层囊泡，其中两个紧密相连的 FeO-Au NPs 层以相反的方向附着。通过进行一系列数值模拟，阐明了双层囊泡的自组装机制。通过计算结果和实验数据验证了双层囊泡的增强光学性质。由于粒子间的磁偶极相互作用和等离子体耦合，双层囊泡表现出比单个 JNPs 更高的 T1 弛豫率和光声特性。特别是，由于 pH 响应性，双层囊泡在酸性肿瘤环境中会分解成单个 JNPs，激活接枝的 PLHP 与从 FeO NPs 释放的二价铁（Fe）之间的细胞内生化反应，导致高效的局部 ROS 生成和增加的细胞内氧化应激。结合阿霉素（DOX）的释放，双层囊泡结合了 ROS 介导的细胞毒性和 DOX 诱导的化疗，与单药治疗相比，大大提高了治疗效果。通过放射性同位素 Cu 标记的囊泡的正电子发射断层扫描（PET）成像也证实了高肿瘤积累效率和快速从体内清除囊泡。
