title: Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D Tumor Platform.
abstract: Overcoming transport barriers to delivery of therapeutic agents in tumors remains a major challenge. Focused ultrasound (FUS), in combination with modern nanomedicine drug formulations, offers the ability to maximize drug transport to tumor tissue while minimizing toxicity to normal tissue. This potential remains unfulfilled due to the limitations of current approaches in accurately assessing and quantifying how FUS modulates drug transport in solid tumors. A novel acoustofluidic platform is developed by integrating a physiologically relevant 3D microfluidic device and a FUS system with a closed-loop controller to study drug transport and assess the response of cancer cells to chemotherapy in real time using live cell microscopy. FUS-induced heating triggers local release of the chemotherapeutic agent doxorubicin from a liposomal carrier and results in higher cellular drug uptake in the FUS focal region. This differential drug uptake induces locally confined DNA damage and glioblastoma cell death in the 3D environment. The capabilities of acoustofluidics for accurate control of drug release and monitoring of localized cell response are demonstrated in a 3D in vitro tumor mode. This has important implications for developing novel strategies to deliver therapeutic agents directly to the tumor tissue while sparing healthy tissue.
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Ave, C1/501, Boston, MA, 02115, USA.
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Zervantonakis
authors.affiliation: Department of Radiology, Harvard Medical School, Brigham and Women's Hospital, 221 Longwood Ave 514a, Boston, MA, 02115, USA.
authors.forename: Costas D
authors.initials: CD
authors.lastname: Arvanitis
mesh_terms: D000162:Acoustics / Q000295:instrumentation; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D061249:Batch Cell Culture Techniques / Q000295:instrumentation; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D016903:Drug Monitoring / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D017022:Flow Injection Analysis / Q000295:instrumentation*; D006801:Humans; D056656:Lab-On-A-Chip Devices; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D066330:Printing, Three-Dimensional / Q000295:instrumentation; D013010:Sonication / Q000295:instrumentation*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations
keywords: acoustofluidics; controlled release; drug delivery; focused ultrasound; tumor microenvironments