title: Microvessels-on-a-Chip to Assess Targeted Ultrasound-Assisted Drug Delivery.
abstract: Microbubbles have been used in ultrasound-assisted drug delivery to help target solid tumors via blood vessels in vivo; however, studies to understand the phenomena at the cellular level and to optimize parameters for ultrasound or microbubbles in vivo are challenging and expensive to perform. Here, we utilize microfluidic microvessels-on-a-chip that enable visualization of microbubble/ultrasound-dependent drug delivery to microvasculature. When exposed to pulsed ultrasound, microbubbles perfused through microvessels-on-a-chip were observed to stably oscillate. Minimal cellular damage was observed for both microbubbles and untargeted doxorubicin-encapsulating liposomes (DOX-liposomes) perfused through chip microvessels. In contrast, passive and ultrasound-assisted perfusion of integrin-targeted DOX-liposomes induced cytotoxicity, which was only significantly enhanced for ultrasound-assisted perfusion when microbubbles were coperfused. These results suggest that stably oscillating microbubbles enhance targeted DOX-liposome internalization/cytotoxicity largely by stimulating integrin receptor endocytosis. Furthermore, our study demonstrates the utility of our microvessels-on-a-chip as a screening platform for optimizing drug dosage, targeting ligands and drugs.
authors: Department of Biomedical Engineering, Boston University , 44 Cummington Mall, Boston, Massachusetts 02215, United States.
authors: Yoonjee C
authors: YC
authors: Park
authors: Department of Biomedical Engineering, Boston University , 44 Cummington Mall, Boston, Massachusetts 02215, United States.
authors: Chentian
authors: C
authors: Zhang
authors: School of Mechanical and Aerospace Engineering, Seoul National University , Seoul 151-744, Korea.
authors: Sudong
authors: S
authors: Kim
authors: Department of Biomedical Engineering, Boston University , 44 Cummington Mall, Boston, Massachusetts 02215, United States.
authors: Graciela
authors: G
authors: Mohamedi
authors: Department of Biomedical Engineering, Boston University , 44 Cummington Mall, Boston, Massachusetts 02215, United States.
authors: Carl
authors: C
authors: Beigie
authors: NanoValent Pharmaceuticals, Inc. , 910 Technology Boulevard, Suite G, Bozeman, Montana 59718, United States.
authors: Jon O
authors: JO
authors: Nagy
authors: Department of Mechanical Engineering, Boston University , Boston, Massachusetts 02215, United States.
authors: R Glynn
authors: RG
authors: Holt
authors: Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford , Old Road Campus Research Building, Oxford OX3 7DQ, United Kingdom.
authors: Robin O
authors: RO
authors: Cleveland
authors: School of Mechanical and Aerospace Engineering, Seoul National University , Seoul 151-744, Korea.
authors: Noo Li
authors: NL
authors: Jeon
authors: Department of Biomedical Engineering, Boston University , 44 Cummington Mall, Boston, Massachusetts 02215, United States.|Division of Materials Science and Engineering, Boston University , Boston, Massachusetts 02215, United States.
authors: Joyce Y
authors: JY
authors: Wong
mesh_terms: D004317:Doxorubicin; D016503:Drug Delivery Systems; D008081:Liposomes; D045423:Microbubbles; D055806:Microvessels; D014465:Ultrasonics
chemical_list: D008081:Liposomes; D004317:Doxorubicin
keywords: antiangiogenesis; focused-ultrasound; microvasculature-on-a-chip; targeted drug delivery; ultrasound-assisted drug delivery