title: Stereotactic modulation of blood-brain barrier permeability to enhance drug delivery.
abstract: Drug delivery in the CNS is limited by endothelial tight junctions forming the impermeable blood-brain barrier. The development of new treatment paradigms has previously been hampered by the restrictiveness of the blood-brain barrier to systemically administered therapeutics. With recent advances in stereotactic localization and noninvasive imaging, we have honed the ability to modulate, ablate, and rewire millimetric brain structures to precisely permeate the impregnable barrier. The wide range of focused radiations offers endless possibilities to disrupt endothelial permeability with different patterns and intensity following 3-dimensional coordinates offering a new world of possibilities to access the CNS, as well as to target therapies. We propose a review of the current state of knowledge in targeted drug delivery using noninvasive image-guided approaches. To this end, we focus on strategies currently used in clinics or in clinical trials such as targeted radiotherapy and magnetic resonance guided focused ultrasound, but also on more experimental approaches such as magnetically heated nanoparticles, electric fields, and lasers, techniques which demonstrated remarkable results both in vitro and in vivo. We envision that biodistribution and efficacy of systemically administered drugs will be enhanced with further developments of these promising strategies. Besides therapeutic applications, stereotactic platforms can be highly valuable in clinical applications for interventional strategies that can improve the targetability and efficacy of drugs and macromolecules. It is our hope that by showcasing and reviewing the current state of this field, we can lay the groundwork to guide future research in this realm.
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Geoff
authors.initials: G
authors.lastname: Appelboom
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Alexandre
authors.initials: A
authors.lastname: Detappe
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Melissa
authors.initials: M
authors.lastname: LoPresti
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Sijumon
authors.initials: S
authors.lastname: Kunjachan
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Mitrasinovic
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Serge
authors.initials: S
authors.lastname: Goldman
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Steve D
authors.initials: SD
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Stanford Medical Center, Stanford, California (G.A., S.D.C.); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts (A.D., S.K.); Institut Lumière Matière, Université Claude Bernard Lyon 1, Villeurbanne, France (A.D., O.T.); Department of Neurosurgery, Baylor College of Medicine, Houston, Texas (M.L.); Department of Neurological Surgery, Columbia University Medical Center, New York, New York (S.M.); Department of Nuclear Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium (S.G.).
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000528:radiation effects; D002199:Capillary Permeability; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D053685:Laser Therapy / Q000379:methods; D055909:Magnetic Field Therapy / Q000379:methods; D053758:Nanoparticles / Q000627:therapeutic use; D016634:Radiosurgery / Q000379:methods; D013238:Stereotaxic Techniques; D014464:Ultrasonic Therapy / Q000379:methods
keywords: electroporation; focused ultrasound; microbubbles; photodynamic therapy; vascular permeability