Chymotrypsin etched ultrasmall gold nanoclusters for dual response diagnosis and deeply penetrated chemodynamic therapy of pancreatic cancer

Pancreatic cancer (PC) is a highly invisible malignancy for which the early diagnosis is crucial to achieve the best treatment outcome. Abnormalities in serum chymotrypsin (ChT) are commonly associated with the development of PC, suggesting its potential role as a novel biomarker candidate. Herein, we report a ChT-responsive ultrasmall apo catalase-stabilized gold nanoclusters (AuCATapo NCs, core size ~2nm) with remarkable fluorescence and peroxidase (POD)-like activity. It can achieve "fluorescence" and "colorimetric" dual detection of ChT, with a wide detection range (0 – 100μg/mL) and a low detection limit (0.029μg/mL). Additionally, the weak acidity (pH 6.2 – 6.8) in the tumor microenvironment can meet the optimal catalytic capacity of deeply penetrated AuCATapo NCs, which generates cytotoxic reactive oxygen species to cause thorough tumor damage effects. The ChT-cleaved AuCATapo NCs may expose more catalytic active sites, resulting in higher tumor cytotoxicity, as demonstrated in both in vitro and in vivo models. Generally, these NCs probes can simultaneously realize accurate detection of ChT and efficient pancreatic tumor ablation via nanozyme based catalytic therapy, opening up a new idea of "diagnosis and treatment integration" for PC.