TY - JOUR
T1 - Effects of tumor microenvironments on targeted delivery of glycol chitosan nanoparticles
AU - Yhee, Ji Young
AU - Jeon, Sangmin
AU - Yoon, Hong Yeol
AU - Shim, Man Kyu
AU - Ko, Hyewon
AU - Min, Jiwoong
AU - Na, Jin Hee
AU - Chang, Hyeyoun
AU - Han, Hyounkoo
AU - Kim, Jong Ho
AU - Suh, Minah
AU - Lee, Hyukjin
AU - Park, Jae Hyung
AU - Kim, Kwangmeyung
AU - Kwon, Ick Chan
N1 - Funding Information:
This work was supported by the GiRC ( NRF-2012K1A1A2A01055811 ), the GRL project ( NRF-2013K1A1A2A02050115 ), the KU-KIST project and the Intramural Research Program of KIST.
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/12/10
Y1 - 2017/12/10
N2 - In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated. Herein, ectopic subcutaneous tumor models presenting different tumor microenvironments were established by inoculation of SCC7, U87, HT29, PC3, and A549 cancer cell lines into athymic nude mice, respectively. In the five different types of tumor-bearing mice, tumor-targeted delivery of self-assembled glycol chitosan nanoparticles (CNPs) were comparatively evaluated to identify the correlation between the tumor microenvironments and targeted delivery of CNPs. As a result, neovascularization and extents of intratumoral extracellular matrix (ECM) were both important in determining the tumor targeted delivery of CNPs. The EPR effect was maximized in the tumors which include large extent of angiogenic blood vessels and low intratumoral ECM content. This comprehensive study provides substantial evidence that the EPR effects based tumor-targeted delivery of nanoparticles can be different depending on the tumor microenvironment in individual tumors. To overcome current limitations in clinical nanomedicine, the tumor microenvironment of the patients and EPR effects in clinical tumors should also be carefully studied.
AB - In cancer theranostics, the main strategy of nanoparticle-based targeted delivery system has been understood by enhanced permeability and retention (EPR) effect of macromolecules. Studies on diverse nanoparticles provide a better understanding of different EPR effects depending on their structure, physicochemical properties, and chemical modifications. Recently the tumor microenvironment has been considered as another important factor for determining tumor-targeted delivery of nanoparticles, but the correlation between EPR effects and tumor microenvironment has not yet been fully elucidated. Herein, ectopic subcutaneous tumor models presenting different tumor microenvironments were established by inoculation of SCC7, U87, HT29, PC3, and A549 cancer cell lines into athymic nude mice, respectively. In the five different types of tumor-bearing mice, tumor-targeted delivery of self-assembled glycol chitosan nanoparticles (CNPs) were comparatively evaluated to identify the correlation between the tumor microenvironments and targeted delivery of CNPs. As a result, neovascularization and extents of intratumoral extracellular matrix (ECM) were both important in determining the tumor targeted delivery of CNPs. The EPR effect was maximized in the tumors which include large extent of angiogenic blood vessels and low intratumoral ECM content. This comprehensive study provides substantial evidence that the EPR effects based tumor-targeted delivery of nanoparticles can be different depending on the tumor microenvironment in individual tumors. To overcome current limitations in clinical nanomedicine, the tumor microenvironment of the patients and EPR effects in clinical tumors should also be carefully studied.
KW - Enhanced permeability and retention effects
KW - Glycol chitosan
KW - Nanoparticle
KW - Tumor microenvironment
KW - Tumor-targeted delivery
UR - http://www.scopus.com/inward/record.url?scp=85033666235&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2017.09.015
DO - 10.1016/j.jconrel.2017.09.015
M3 - Article
C2 - 28917532
AN - SCOPUS:85033666235
SN - 0168-3659
VL - 267
SP - 223
EP - 231
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -