title: Drug penetration and metabolism in 3D cell cultures treated in a 3D printed fluidic device: assessment of irinotecan via MALDI imaging mass spectrometry.
abstract: Realistic in vitro models are critical in the drug development process. In this study, a novel in vitro platform is employed to assess drug penetration and metabolism. This platform, which utilizes a 3D printed fluidic device, allows for dynamic dosing of three dimensional cell cultures, also known as spheroids. The penetration of the chemotherapeutic irinotecan into HCT 116 colon cancer spheroids was examined with MALDI imaging mass spectrometry (IMS). The active metabolite of irinotecan, SN-38, was also detected. After twenty-four hours of treatment, SN-38 was concentrated to the outside of the spheroid, a region of actively dividing cells. The irinotecan prodrug localization contrasted with SN-38 and was concentrated to the necrotic core of the spheroids, a region containing mostly dead and dying cells. These results demonstrate that this unique in vitro platform is an effective means to assess drug penetration and metabolism in 3D cell cultures. This innovative system can have a transformative impact on the preclinical evaluation of drug candidates due to its cost effectiveness and high throughput.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.|Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, USA.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: LaBonia
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI, USA.
authors.forename: Sarah Y
authors.initials: SY
authors.lastname: Lockwood
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Heller
authors.affiliation: Department of Chemistry, Michigan State University, East Lansing, MI, USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Spence
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.|Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, USA.
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Hummon
mesh_terms: D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification; D018929:Cell Culture Techniques / Q000379:methods; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D000077146:Irinotecan; D056656:Lab-On-A-Chip Devices; D066330:Printing, Three-Dimensional / Q000295:instrumentation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000077146:Irinotecan; D002166:Camptothecin
keywords: 3D cell culture; Biomedicine; HCT 116; In vitro pharmacokinetics; Irinotecan; MALDI imaging mass spectrometry; SN-38