Photodynamic therapy (
PDT) holds great promise in
tumor treatment. Nevertheless, it remains highly desirable to develop easy-to-fabricated
PDT systems with improved
tumor accumulation/internalization and timely therapeutic feedback. Here, we report a
tumor-acidity-responsive chimeric
peptide for enhanced
PDT and noninvasive real-time apoptosis imaging. Both in vitro and in vivo studies revealed that a
tumor mildly acidic microenvironment could trigger rapid protonation of carboxylate
anions in chimeric
peptide, which led to increased ΞΆ potential, improved hydrophobicity, controlled size enlargement, and precise morphology switching from sphere to spherocylinder shape of the chimeric
peptide. All of these factors realized superfast accumulation and prolonged retention in the
tumor region, selective cellular internalization, and enhanced
PDT against the
tumor. Meanwhile, this chimeric
peptide could further generate
reactive oxygen species and initiate cell apoptosis during
PDT. The subsequent formation of
caspase-3 enzyme hydrolyzed the chimeric
peptide, achieving a high signal/noise ratio and timely fluorescence feedback. Importantly, direct utilization of the acidity responsiveness of a biofunctional
Asp-Glu-Val-
Asp-Gly (DEVDG,
caspase-3 enzyme substrate)
peptide sequence dramatically simplified the preparation and increased the performance of the chimeric
peptide furthest.