Bioactive nanofibers covered stent with matched mechanics and durable gemcitabine release for treating esophageal cancer

Abstract

Abstract Developing a drug-eluting esophageal stent (DEES), which provides both mechanical support and local chemotherapy, represents a preferred treatment option for patients with advanced esophageal cancer. However, existing DEES have limitations such as drug loading via surface micro/nano-structures or physical blending of drugs into polymer covering, often lead to issues like initial burst release, short-lasting therapeutic effects, or compromised mechanical properties. To address the above challenges, we synthesized gemcitabine (GEM) blocked biodegradable polyurethane (PG) and then covered it around the surface of NiTi stent via electrospinning to form nanofibers covered stent. This electrospun PG nanofibers achieved firm adhesion without compromising the original mechanical integrity of NiTi stent. In vitro data demonstrated that the PG fibers presented prominent antitumor therapy effect and antiangiogenesis ability, as well as enabled degradation-associated drug release, resulting in less than 1% initial burst release within 24 hours and sustained release over 24 weeks. In vivo assessments indicated the PG fibers could continuously inhibit tumor growth by inducing tumor cell apoptosis and suppressing tumor angiogenesis. This study demonstrates the bioactive nanofibers covered stent with matched mechanics and durable efficacious antitumor, which could offer a potential strategy for treating esophageal cancer via local chemotherapy.