Anticancer Effect of Locally Applicable Aptamer-Conjugated Gemcitabine-Loaded Atelocollagen Patch in Pancreatic Cancer Patient-Derived Xenograft Models

Abstract

Introduction: We investigated the anticancer effect of the aptamer-conjugated gemcitabine loaded atelocollagen patch in pancreatic cancer patient-derived xenograft model to propose a future potential adjuvant surgical strategy during curative pancreatic resection for pancreatic cancer. Method: Pancreatic cancer PDX model was established. Animals were grouped randomly (4∼9 mice per group, with 2 patient tumors) into no treatment control group, treated group with intraperitoneal Gemcitabine injection (IP-GEM), Aptamer-conjugated-Gemcitabine (APT:GEM) or transplant with 3 kinds of Patchs: Atelocollagen-Aptamer-Gemcitibin (Patch I), Atelocollagen-inactive Aptamer-Gemcitibine (Patch II), and Atelocollagen-Gemcitabine (Patch III). Tumor response was evaluated based on histological analysis by H&E staining and IHC was performed. Anticancer therapy-related toxicity was evaluated by hematologic finding. Results: Patch I group (necleolin-aptamer conjugated gemcitabine loaded atelocollagen-patch) showed the most significant reduction of tumor growth rate, comparing with no treatment group (p<0.05). However, other treatment groups were not found to show significant reduction in tumor growth rate (0.05< p <0.1). Patch I group also showed significant apoptotic process, but TUNNEL positive cancer cells were found along the superficial layer of the tumor surface, where therapeutic patch had been applied. There were no microscopic evidences suggesting potential toxicity, such as inflammation nor necrotic changes, in liver, lung, kidney, and spleen tissue. In addition, no leukopenia, no anemia, and no neutropenia were observed in Patch I group. Conclusions: This new implantable aptamer-drug conjugate system is thought to be new surgical strategy to augment the oncologic significance of margin-negative resection in treating pancreatic cancer in near future.