한빛사논문
- 조회357
Sangmin Jeon a,1, Eunsung Jun c,d,1, Hyeyoun Chang a,1, Ji Young Yhee a,f, Eun-Young Koh c, Yeounhee Kim c, Jae Yun Jung e, Eun Ji Jeong e, Jong Won Lee a,b, Man Kyu Shim a, Hong Yeol Yoon a, Suhwan Chang e,*, Kwangmeyung Kim a,b,g,*, Song Cheol Kim d,*
a Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, 5, Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea b KU-KIST Graduate School of Converging Science and Technology, Korea University, 1 Anam-dong, Seongbuk-gu, Seoul 136-701, Republic of Korea c Department of Convergence Medicine, Asan Institute for Life Sciences, University of Ulsan College of Medicine and Asan Medical Center, Seoul 05505, Republic of Korea d Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Asan Medical Center, AMIST, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea e Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, South Korea f Green Vet, 131-1 Ihyeon-ro 30beon-gil, Giheung-gu, Yongin-si, Gyeonggi-do 16924, Republic of Korea g College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
* Corresponding authors.
1 The authors contributed equally to this paper
Abstract
Many preclinically tested nanoparticles in existing animal models fail to be directly translated into clinical applications because of their poor resemblance to human cancer. Herein, the enhanced permeation and retention (EPR) effect of glycol chitosan nanoparticles (CNPs) in different tumor microenvironments (TMEs) was compared using different pancreatic tumor models, including pancreatic cancer cell line (BxPC3), patient-derived cancer cell (PDC), and patient-derived xenograft (PDX) models. CNPs were intravenously injected into different tumor models, and their accumulation efficiency was evaluated using non-invasive near-infrared fluorescence (NIRF) imaging. In particular, differences in angiogenic vessel density, collagen matrix, and hyaluronic acid content in tumor tissues of the BxPC3, PDC, and PDX models greatly affected the tumor-targeting efficiency of CNPs. In addition, different PDX models were established using different tumor tissues of patients to predict the clinical EPR effect of CNPs in inter-patient TMEs, wherein the gene expression levels of PECAM1, COL4A1, and HAS1 in human tumor tissues were observed to be closely related to the EPR effect of CNPs in PDX models. The results suggested that the PDX models could mimic inter-patient TMEs with different blood vessel structures and extracellular matrix (ECM) content that critically affect the tumor-targeting ability of CNPs in different pancreatic PDX models. This study provides a better understanding of the heterogeneity and complexity of inter-patient TMEs that can predict the response of various nanoparticles in individual tumors for personalized cancer therapy.
논문정보
- Research article
- 2022년 09월 (BRIC 등록일 2022-10-04)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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