Development of an Electro-Responsive Sorafenib-Loaded Polypyrrole Coating-Modified Nickel-Titanium Alloy for Tumor...

Nickel-titanium (NiTi) stents have been widely used for the palliative management of portal vein tumor thrombosis (PVTT) due to their excellent mechanical strength and biocompatibility. However, conventional NiTi implants are therapeutically passive and lack intrinsic antitumor activity, rendering them vulnerable to tumor ingrowth and subsequent restenosis. Electrical stimulation-mediated ablation offers a controllable physical strategy for local tumor clearance; however, the native TiO₂ passivation layer on the NiTi surface restricts its interfacial electroactivity. Electrochemical impedance spectroscopy revealed that the PPy coating significantly reduced the interfacial impedance of the NiTi substrate. After loading with sorafenib, NiTi-PPy-S maintained good electrochemical responsiveness and enabled voltage-dependent drug release characteristics. Under an applied potential of 0.9 V for 24 h, approximately 10.522 ± 0.295 μg/cm² of the loaded sorafenib was released mechanistically, whereas only 0.249 ± 0.171 μg/cm² was released through passive diffusion over the same period. The antitumor effect is closely associated with ES-triggered Ca²⁺ influx, mitochondrial Ca²⁺ overload, loss of mitochondrial membrane potential, and caspase-3-dependent apoptosis. These findings demonstrate that electro-responsive PPy can transform passive NiTi implants into active antitumor therapeutic interfaces, offering a promising strategy for developing multifunctional implants for PVTT treatment.