Niu Jie, Yu Jie, Wu Xuan, Zhang Ying-Ming, Chen Yong, Yu Zhilin, Liu Yu
College of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University Tianjin 300071 P. R. China
School of Chemistry and Chemical Engineering, Yangzhou University Yangzhou Jiangsu 225002 P. R. China.
Chem Sci. 2024 Aug 5;15(34):13779-13787. doi: 10.1039/d4sc04261a. eCollection 2024 Aug 28.
The manipulation of biocompatible supramolecular nanostructures at subcellular and cellular levels has become one of the increasingly significant topics but remains a formidable challenge in chemical and biological science. In this work, a controllable supramolecular aggregate based on host-guest competitive binding is elaborately constructed using cucurbit[8]uril, methionine-containing amphiphilic peptide, and perylene diimide, displaying oxidation-driven macrocycle-confined fluorescence enhancement for cell imaging and morphological reconstruction for cancer cell death. The experimental results demonstrate that cucurbit[8]uril possesses a high binding affinity with the methionine peptide, while this value sharply decreases after the methionine residue is oxidized to sulfoxide or sulfone. Therefore, perylene diimide can be competitively included by cucurbit[8]uril in the co-assemblies, eventually resulting in a 10-fold fluorescence enhancement and the conversion of topological morphology from nano-sized particles to micron-sized sheets. Moreover, the obtained ternary assemblies can be oxidized by endogenous reactive oxygen species in cancer cells, thus not only providing enhanced fluorescence for cell imaging, but also leading to endoplasmic reticulum dysfunction and significant cell death. Therefore, the controllable and oxidation-responsive morphological transformation based on the host-guest competitive binding in biological media can be viewed as a feasible means for efficient disease theragnosis.
在亚细胞和细胞水平上对生物相容性超分子纳米结构进行操控已成为日益重要的课题之一，但在化学和生物科学领域仍是一项艰巨的挑战。在这项工作中，基于主客体竞争结合精心构建了一种可控的超分子聚集体，它由葫芦[8]脲、含蛋氨酸的两亲性肽和苝二酰亚胺组成，表现出氧化驱动的大环限制荧光增强用于细胞成像以及癌细胞死亡的形态重建。实验结果表明，葫芦[8]脲与蛋氨酸肽具有高结合亲和力，而蛋氨酸残基氧化为亚砜或砜后该值急剧下降。因此，在共组装体中苝二酰亚胺可被葫芦[8]脲竞争性包合，最终导致荧光增强10倍以及拓扑形态从纳米级颗粒转变为微米级片层。此外，所获得的三元组装体可被癌细胞内源性活性氧氧化，不仅为细胞成像提供增强的荧光，还导致内质网功能障碍和显著的细胞死亡。因此，基于生物介质中主客体竞争结合的可控且氧化响应的形态转变可被视为高效疾病诊疗的一种可行手段。
