TY - JOUR
T1 - Prediction the clinical EPR effect of nanoparticles in patient-derived xenograft models
AU - Jeon, Sangmin
AU - Jun, Eunsung
AU - Chang, Hyeyoun
AU - Yhee, Ji Young
AU - Koh, Eun Young
AU - Kim, Yeounhee
AU - Jung, Jae Yun
AU - Jeong, Eun Ji
AU - Lee, Jong Won
AU - Shim, Man Kyu
AU - Yoon, Hong Yeol
AU - Chang, Suhwan
AU - Kim, Kwangmeyung
AU - Kim, Song Cheol
N1 - Funding Information:
This study was supported by a grant ( 2021IP0020 ) from the Asan Institute for Life Sciences, Asan Medical Center , Seoul, Korea, a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare , Republic of Korea ( HI14C2640 ), a grant from the National Research Foundation (NRF) of Korea, funded by the Ministry of Science ( NRF-2019R1A2C3006283 ), the KU-KIST Graduate School of Converging Science and Technology ( Korea University ), and the Intramural Research Program of KIST .
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/11
Y1 - 2022/11
N2 - 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.
AB - 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.
KW - EPR effect
KW - Nanoparticles
KW - Patient-derived xenograft model
KW - Tumor heterogeneity
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85138176295&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2022.09.007
DO - 10.1016/j.jconrel.2022.09.007
M3 - Article
C2 - 36089170
AN - SCOPUS:85138176295
SN - 0168-3659
VL - 351
SP - 37
EP - 49
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -