title: Characterization of Cell-Type-Specific Drug Transport and Resistance of Breast Cancers Using Tumor-Microenvironment-on-Chip.
abstract: Heterogeneous response and resistance of cancer cells to chemotherapeutic drugs pose a significant challenge for successful cancer treatments. In this study, an integrated experimental and theoretical analysis of cellular drug transport was developed. The experimental platform, called tumor-microenvironment-on-chip (T-MOC), is a microfluidic platform where cancer cells were cultured within a three-dimensional extracellular matrix perfused with interstitial fluid. Three types of human breast cancer cell lines (MCF-7, MDA-MB-231, and SUM-159PT) were cultured on this T-MOC platform, and their drug response and resistance to doxorubicin were characterized by time-lapse quantitative fluorescence microscopy. To study the effects of nanoparticle-mediated drug delivery, the transport and action of doxorubicin encapsulated nanoparticles were also examined. Based on the experimental data obtained, a theoretical model was developed to quantify and ultimately predict the cellular transport processes of drugs cell-type specifically. The results demonstrate that the cellular drug transport can be cell-type-specifically quantified by rate constants representing the uptake and efflux of doxorubicin across the cellular membrane.
authors.affiliation: School of Mechanical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Kyeonggon
authors.initials: K
authors.lastname: Shin
authors.affiliation: School of Mechanical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Brett S
authors.initials: BS
authors.lastname: Klosterhoff
authors.affiliation: School of Mechanical Engineering, Purdue University , West Lafayette, Indiana 47907, United States.|Weldon School of Biomedical Engineering, Birck Nanotechnology Center, and Purdue Center for Cancer Research, Purdue University , West Lafayette, Indiana 47907, United States.
authors.forename: Bumsoo
authors.initials: B
authors.lastname: Han
mesh_terms: D001692:Biological Transport / Q000502:physiology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry; D059016:Tumor Microenvironment / Q000187:drug effects*
chemical_list: D004337:Drug Carriers; D004317:Doxorubicin
keywords: breast cancer; cellular pharmacokinetics; doxorubicin; nanoparticles; tumor-microenvironment-on-chip