TY - JOUR
T1 - Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip
AU - Kwak, Bongseop
AU - Ozcelikkale, Altug
AU - Shin, Crystal S.
AU - Park, Kinam
AU - Han, Bumsoo
N1 - Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2014/11/28
Y1 - 2014/11/28
N2 - Delivery of therapeutic agents selectively to tumor tissue, which is referred as "targeted delivery," is one of the most ardently pursued goals of cancer therapy. Recent advances in nanotechnology enable numerous types of nanoparticles (NPs) whose properties can be designed for targeted delivery to tumors. In spite of promising early results, the delivery and therapeutic efficacy of the majority of NPs are still quite limited. This is mainly attributed to the limitation of currently available tumor models to test these NPs and systematically study the effects of complex transport and pathophysiological barriers around the tumors. In this study, thus, we developed a new in vitro tumor model to recapitulate the tumor microenvironment determining the transport around tumors. This model, named tumor-microenvironment-on-chip (T-MOC), consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid. Using this T-MOC platform, the transport of NPs and its variation due to tumor microenvironmental parameters have been studied including cut-off pore size, interstitial fluid pressure, and tumor tissue microstructure. The results suggest that T-MOC is capable of simulating the complex transport around the tumor, and providing detailed information about NP transport behavior. This finding confirms that NPs should be designed considering their dynamic interactions with tumor microenvironment.
AB - Delivery of therapeutic agents selectively to tumor tissue, which is referred as "targeted delivery," is one of the most ardently pursued goals of cancer therapy. Recent advances in nanotechnology enable numerous types of nanoparticles (NPs) whose properties can be designed for targeted delivery to tumors. In spite of promising early results, the delivery and therapeutic efficacy of the majority of NPs are still quite limited. This is mainly attributed to the limitation of currently available tumor models to test these NPs and systematically study the effects of complex transport and pathophysiological barriers around the tumors. In this study, thus, we developed a new in vitro tumor model to recapitulate the tumor microenvironment determining the transport around tumors. This model, named tumor-microenvironment-on-chip (T-MOC), consists of 3-dimensional microfluidic channels where tumor cells and endothelial cells are cultured within extracellular matrix under perfusion of interstitial fluid. Using this T-MOC platform, the transport of NPs and its variation due to tumor microenvironmental parameters have been studied including cut-off pore size, interstitial fluid pressure, and tumor tissue microstructure. The results suggest that T-MOC is capable of simulating the complex transport around the tumor, and providing detailed information about NP transport behavior. This finding confirms that NPs should be designed considering their dynamic interactions with tumor microenvironment.
KW - Cancer
KW - Microfluidics
KW - Nanoparticle transport
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84907195226&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907195226&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2014.08.027
DO - 10.1016/j.jconrel.2014.08.027
M3 - Article
C2 - 25194778
AN - SCOPUS:84907195226
SN - 0168-3659
VL - 194
SP - 157
EP - 167
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -