Sequential assembled chimeric peptide for precise synergistic phototherapy and photoacoustic imaging of tumor apoptosis

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.