Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood–tumor barrier disruption

^aSchool of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332;
^bDepartment of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332;
^cEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114;
^dDepartment of Chemical and Biological Engineering, Tufts University, Medford, MA 02155;
^eCentre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh EH16 4UX, United Kingdom;
^fDepartment of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115

Contributed by Rakesh K. Jain, July 28, 2018 (sent for review April 27, 2018; reviewed by Katherine W. Ferrara and Richard J. Price)

Footnotes

↵¹C.D.A. and V.A. contributed equally to this work.
↵²To whom correspondence may be addressed. Email: costas.arvanitis{at}gatech.edu or jain{at}steele.mgh.harvard.edu.
↵³Present address: Department of Oncology, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.

Author contributions: C.D.A., V.A., and R.K.J. designed research; C.D.A., V.A., Y.G., M.D., J.K., M.O.B., D.F., and R.K.J. performed research; C.D.A., V.A., G.B.F., N.M., and R.K.J. contributed new reagents/analytic tools; C.D.A., V.A., Y.G., M.D., and R.K.J. analyzed data; and C.D.A., V.A., Y.G., M.O.B., and R.K.J. wrote the paper.
Reviewers: K.W.F., Stanford University; and R.J.P., University of Virginia.
Conflict of interest statement: R.K.J. received an honorarium from Amgen and consultant fees from Merck, Ophthotech, Pfizer, SPARC, SynDevRx, and XTuit; owns equity in Enlight, Ophthotech, SynDevRx, and XTuit; served on the Board of Directors of XTuit; and serves on the Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund, and Tekla World Healthcare Fund. Neither any reagent nor any funding from these organizations was used in this study.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1807105115/-/DCSupplemental.