Although considerable progress has been made in nanomedicine, it is still of great significance for nanomedicine machines with natural targeting, diverse functions, maximum drug utilization, and outstanding performance. In this work, a simple small molecule chimeric peptide with the capability of sequential two-step self-assembly was developed. This chimeric peptide could be self-assembled into larger nanoparticles from smaller nanoparticles at tumor extracellular acidic microenvironment and further aggregated in apoptotic tumor cells mediated by photodynamic therapy. In addition to the nanostructure changes, the increasing of size could accelerate cell internalization and tumor accumulation of chimeric peptide for better photodynamic therapy. And the aggregation in the apoptotic cell could enhance the photothermal effect and photoacoustic signal of chimeric peptide for further photothermal therapy and photoacoustic imaging of tumor apoptosis. Both in vitro and in vivo studies demonstrated that these self-assembly behaviors endowed chimeric peptide with well tumor accumulation, preferable tumor suppression, and precise therapeutic evaluation, which should provide a new way for the construction of efficient theranostic agent based on chimeric peptides.

尽管纳米医学取得了长足的进步，但对于具有自然靶向性、功能多样、药物利用率最高、性能优异的纳米医学机器仍然具有重要意义。在这项工作中，开发了一种具有连续两步自组装能力的简单小分子嵌合肽。这种嵌合肽可以在肿瘤细胞外酸性微环境中从较小的纳米颗粒自组装成较大的纳米颗粒，并在光动力疗法介导的凋亡肿瘤细胞中进一步聚集。除了纳米结构的变化，尺寸的增加可以加速嵌合肽的细胞内化和肿瘤积累，以实现更好的光动力治疗。凋亡细胞中的聚集可以增强嵌合肽的光热效应和光声信号，用于进一步光热治疗和肿瘤细胞凋亡的光声成像。体外和体内研究表明，这些自组装行为使嵌合肽具有良好的肿瘤积累、较好的肿瘤抑制作用和精确的治疗评价，这将为构建基于嵌合肽的高效治疗诊断剂提供新途径。