Anticancer effect of locally applicable aptamer-conjugated gemcitabine-loaded atelocollagen patch in pancreatic cancer patient-derived xenograft models

Abstract

We investigated the anticancer effect of the aptamer-conjugated gemcitabine-loaded atelocollagen patch in a pancreatic cancer patient-derived xenograft (PDX) model to propose a future potential adjuvant surgical strategy during curative pancreatic resection for pancreatic cancer. A pancreatic cancer PDX model was established. Animals were grouped randomly into a no-treatment control group; treatment group treated with intraperitoneal gemcitabine injection (IP-GEM) or aptamer-conjugated gemcitabine (APT:GEM); and transplant with three kinds of patches: atelocollagen-aptamer-gemcitabine (patch I), atelocollagen-inactive aptamer-gemcitabine (patch II), and atelocollagen-gemcitabine (patch III). Tumor volumes and response were evaluated based on histological analysis by H&E staining and Immunohistochemistry (IHC) was performed. Anticancer therapy-related toxicity was evaluated by hematologic findings. The patch I group showed the most significant reduction of tumor growth rate, compared with the 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). There was no microscopic evidence suggesting potential toxicity, such as inflammation, nor necrotic changes in liver, lung, kidney, and spleen tissue. In addition, no leukopenia, anemia, or neutropenia was observed in the patch I group. This implantable aptamer-drug conjugate system is thought to be a new surgical strategy to augment the oncologic significance of margin-negative resection in treating pancreatic cancer in near future.