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

 Seung Soo Hong  ;  Sena Lee  ;  Sung Hwan Lee  ;  Seonhowa Kim  ;  Doyoung Kim  ;  Hanseul Park  ;  Jongook Lee  ;  Jung Hwan Lee  ;  Chang Moo Kang 
 CANCER SCIENCE, Vol.113(5) : 1752-1762, 2022-05 
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Animals ; Cell Line, Tumor ; Collagen ; Deoxycytidine / analogs & derivatives ; Disease Models, Animal ; Heterografts ; Humans ; Pancreatic Neoplasms* / drug therapy ; Pancreatic Neoplasms* / pathology ; Xenograft Model Antitumor Assays
PDTX ; PDX ; anticancer drug ; pancreatic cancer ; patient-derived tumor xenograft mouse model
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.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Chang Moo(강창무) ORCID logo https://orcid.org/0000-0002-5382-4658
Hong, Seung Soo(홍승수)
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