A multifunctional Janus-inspired therapeutic patch enabling intraoperative control of tumor dissemination and unidirectional drug delivery
TL;DR
This Janus-inspired patch is designed to bridge surgical resection and localized chemotherapy within a single intraoperative implant, and establishes an effective strategy that bridges surgery and intratumoral chemotherapy for effective postoperative PDAC control.
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.