title: Simulation of complex transport of nanoparticles around a tumor using tumor-microenvironment-on-chip.
abstract: 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.
authors.affiliation: School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Bongseop
authors.initials: B
authors.lastname: Kwak
authors.affiliation: School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Altug
authors.initials: A
authors.lastname: Ozcelikkale
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA.
authors.forename: Crystal S
authors.initials: CS
authors.lastname: Shin
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.affiliation: School of Mechanical Engineering, Purdue University, West Lafayette, IN, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA; Birck Nanotechnology Center, Purdue University, West Lafayette, IN, USA. Electronic address: bumsoo@purdue.edu.
authors.forename: Bumsoo
authors.initials: B
authors.lastname: Han
mesh_terms: D002196:Capillaries / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003198:Computer Simulation; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism / Q000648:ultrastructure; D045604:Extracellular Fluid / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D044085:Microfluidics; D053758:Nanoparticles / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D010316:Particle Size; D059016:Tumor Microenvironment
keywords: Cancer; Microfluidics; Nanoparticle transport; Tumor microenvironment