A multifunctional Janus-inspired therapeutic patch enabling intraoperative control of tumor dissemination and unidirectional drug delivery

Abstract

Postoperative recurrence and metastasis remain formidable challenges in pancreatic ductal adenocarcinoma (PDAC), primarily due to bleeding-driven tumor dissemination and residual microscopic lesions after resection. However, the current surgical operation offers limited intraoperative treatment strategies to prevent these events. Herein, a multifunctional Janus-inspired therapeutic patch (JTP) is designed to bridge surgical resection and localized chemotherapy within a single intraoperative implant. The JTP features a trilayer Janus architecture that enables integrated control over hemostasis, tumor interception, and intratumoral chemotherapy. Specifically, the inner gelatin-hyaluronic acid sponge enables rapid hemostasis (1.24 min) and capture of circulating tumor cells. The middle gemcitabine-loaded polylactic acid nanofiber layer enables sustained and local drug release of gemcitabine (GEM) toward the surgical resection site, while the outer hydrophobic polycaprolactone backing serves as a protective barrier, preventing peritoneal adhesion and drug diffusion in unwanted directions (less than 5%). In an orthotopic PDAC resection model, a single JTP implantation achieved 78% blood loss reduction, ∼89% tumor suppression, and substantial inhibition of hepatic metastasis, extending survival to 38 days with 80% survival rate. By transforming the surgical site into an active therapeutic interface, this Janus-inspired patch establishes an effective strategy that bridges surgery and intratumoral chemotherapy for effective postoperative PDAC control.