Construction of all-in-one peptide nanomedicine with photoacoustic imaging guided mild hyperthermia for enhanced cancer chemotherapy

Engineered nanoplatforms for cancer simultaneous imaging and combinational therapy have emerged as a new trend in cancer theranostics. However, molecular engineering of nanomedicines with structure minimization and function maximization are still in acute famine. In this study, a novel kind of supramolecular peptide nanomedicine with all-in-one property was delicately constructed for tumor photoacoustic imaging (PAI) and chemophotothermal combination therapy. The designed peptide conjugates were easily one-step synthesized with high porphyrin and tyroservatide covalently loading, which self-assembled into supramolecular nanomedicine via non-covalent interactions. Stimulated by the photothermal effect of porphyrin, cancer cells became more susceptive to the chemotherapy drugs of tyroservatide, giving rise to enhanced histone acetylation and cell apoptosis. Moreover, with the assistance of PA imaging guided mild hyperthermia, the in vivo tumor inhibition rate of chemo-photothermal combination therapy with single one injection achieved to 70%, thereby can significantly reduce the doses of chemotherapy. The straightforward preparation process and high biosafety were capable of endowing the designed peptide nanomedicine with great potential for clinical transformation and application. This work provided new insights to fabricate all-in-one supramolecular nanoplatforms based on peptide self-assembly for tumor theranostics.

用于癌症同步成像和联合治疗的工程化纳米平台已成为癌症诊疗一体化的新趋势。然而，具有结构最小化和功能最大化的纳米药物的分子工程仍然极度匮乏。在这项研究中，精心构建了一种具有一体化特性的新型超分子肽纳米药物，用于肿瘤光声成像（PAI）和化学光热联合治疗。所设计的肽偶联物易于一步合成，能共价负载高含量的卟啉和酪丝亮肽，并通过非共价相互作用自组装成超分子纳米药物。受卟啉的光热效应刺激，癌细胞对酪丝亮肽化疗药物变得更加敏感，导致组蛋白乙酰化增强和细胞凋亡。此外，在光声成像引导的温和热疗辅助下，单次注射的化学 - 光热联合治疗的体内肿瘤抑制率达到70%，从而可显著降低化疗剂量。简单的制备过程和高生物安全性使所设计的肽纳米药物具有很大的临床转化和应用潜力。这项工作为基于肽自组装构建用于肿瘤诊疗一体化的一体化超分子纳米平台提供了新的见解。