Pancreatic cancer is a very aggressive type of cancer that usually starts in the cells of the pancreatic duct. This kind of cancer is called pancreatic ductal adenocarcinoma (PDAC), and it makes up more than 90% of all pancreatic cancer cases.
Pancreatic cancer poses a significant health challenge due to its nonspecific early symptoms, delayed diagnosis, and poor response to systemic therapies. Insufficient tumor specificity and the invasiveness of surgical interventions limit current diagnostic and therapeutic approaches. Therefore, researchers have investigated a novel gold nanoparticle-based phototheranostic agent named AuHQ for specific imaging and treatment of pancreatic cancer. AuHQ is composed of gold nanoparticles (AuNPs), an AIE fluorophore (quinoline-malononitrile-COOH), and a pancreatic cancer-specific enzyme-responsive peptide (AGFSLPAGC).
Figure 1. A Pancreatic Cancer-Specific Phototheranostic Regulator Based on AuNPs: The AuHQ Scheme[1].
MMP-2 validate the enzyme responsiveness of AIEgens-tethered Gold Nanoparticles.
Researchers employed MMP-2 as a control enzyme to validate the enzyme responsiveness of AuHQ. This validation was crucial to ensure that AuHQ could specifically trigger self-assembly and photothermal effects in the presence of pancreatic cancer-specific enzymes such as Cathepsin E, thereby allowing for a comparison of the specific cleavage effects of CTSE. Researchers introduced CTSE into a sodium acetate buffer solution (pH 4) and activated it by incubating at 37 °C for 0.5 h. Subsequently, they added AuHQ in PBS solution (pH 5.5) to the activated CTSE and monitored its fluorescence and UV absorption spectra at various incubation times. Additionally, they incubated AuHQ with several enzymes under different conditions for 12 h, including MMP-2, which activated for 2 h at 37 °C in Tris buffer (pH 7.4) with p-aminophenylmercuric.
The fluorescence intensity of AuHQ treated with CTSE significantly increased, indicating that CTSE specifically cleaves the peptide chain in AuHQ, releasing the AIE fluorophore. In contrast, AuHQ treated with MMP-2 showed no significant change in fluorescence intensity, suggesting that MMP-2 lacks specificity for cleaving AuHQ. Moreover, the hydrodynamic particle size of AuHQ treated with CTSE significantly increased, demonstrating that CTSE can trigger the self-assembly of AuHQ into larger particles. Conversely, the particle size of AuHQ treated with MMP-2 remained unchanged, indicating that MMP-2 cannot induce self-assembly of AuHQ.
Consequently, CTSE can specifically cleave the AGFSLPAGC peptide, thereby triggering the dual self-assembly of AuNPs and AIE fluorophores. This mechanism enables AuHQ to achieve highly efficient and precise photothermal-immunotherapy, as well as dual-modal fluorescence-photoacoustic imaging. Moreover, combining AuHQ with an IDO1 inhibitor further enhances its therapeutic efficacy. Thus, AuHQ holds promise as a safe and effective diagnostic and therapeutic approach for pancreatic cancer.
