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Achieving Spatial and Molecular Specificity with Ultrasound-Targeted Biomolecular Nanotherapeutics

Szablowski, Jerzy O. and Bar-Zion, Avinoam and Shapiro, Mikhail G. (2019) Achieving Spatial and Molecular Specificity with Ultrasound-Targeted Biomolecular Nanotherapeutics. Accounts of Chemical Research, 52 (9). pp. 2427-2434. ISSN 0001-4842. https://resolver.caltech.edu/CaltechAUTHORS:20190809-160556043

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Abstract

The precise targeting of cells in deep tissues is one of the primary goals of nanomedicine. However, targeting a specific cellular population within an entire organism is challenging due to off-target effects and the need for deep tissue delivery. Focused ultrasound can reduce off-targeted effects by spatially restricting the delivery or action of molecular constructs to specific anatomical sites. Ultrasound can also increase the efficiency of nanotherapeutic delivery into deep tissues by enhancing the permeability of tissue boundaries, promoting convection, or depositing energy to actuate cellular activity. In this review we focus on the interface between biomolecular engineering and focused ultrasound and describe the applications of this intersection in neuroscience, oncology, and synthetic biology. Ultrasound can be used to trigger the transport of therapeutic payloads into a range of tissues, including specific regions of the brain, where it can be targeted with millimeter precision through intact skull. Locally delivered molecular constructs can then control specific cells and molecular pathways within the targeted region. When combined with viral vectors and engineered neural receptors, this technique enables noninvasive control of specific circuits and behaviors. The penetrant energy of ultrasound can also be used to more directly actuate micro- and nanotherapeutic constructs, including microbubbles, vaporizable nanodroplets, and polymeric nanocups, which nucleate cavitation upon ultrasound exposure, leading to local mechanical effects. In addition, it was recently discovered that a unique class of acoustic biomolecules—genetically encodable nanoscale protein structures called gas vesicles—can be acoustically “detonated” as sources of inertial cavitation. This enables the targeted disruption of selected cells within the area of insonation by gas vesicles that are engineered to bind cell surface receptors. It also facilitates ultrasound-triggered release of molecular payloads from engineered therapeutic cells heterologously expressing intracellular gas vesicles. Finally, focused ultrasound energy can be used to locally elevate tissue temperature and activate temperature-sensitive proteins and pathways. The elevation of temperature allows noninvasive control of gene expression in vivo in cells engineered to express thermal bioswitches. Overall, the intersection of biomolecular engineering, nanomaterials and focused ultrasound can provide unparalleled specificity in controlling, modulating, and treating physiological processes in deep tissues.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/acs.accounts.9b00277DOIArticle
ORCID:
AuthorORCID
Szablowski, Jerzy O.0000-0001-7851-5408
Bar-Zion, Avinoam0000-0002-7564-9467
Shapiro, Mikhail G.0000-0002-0291-4215
Additional Information:© 2019 American Chemical Society. Received: May 25, 2019; Published: August 9, 2019. Accounts of Chemical Research special issue “Nanomedicine and Beyond” Author Contributions: J.O.S. and A.B.-Z. contributed equally. The authors declare no competing financial interest.
Funders:
Funding AgencyGrant Number
NIHR01EB018975
David and Lucile Packard FoundationUNSPECIFIED
Marie Curie FellowshipUNSPECIFIED
Issue or Number:9
Record Number:CaltechAUTHORS:20190809-160556043
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190809-160556043
Official Citation:Achieving Spatial and Molecular Specificity with Ultrasound-Targeted Biomolecular Nanotherapeutics. Jerzy O. Szablowski, Avinoam Bar-Zion, and Mikhail G. Shapiro. Accounts of Chemical Research 2019 52 (9), 2427-2434. DOI: 10.1021/acs.accounts.9b00277
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:97738
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:09 Aug 2019 23:12
Last Modified:03 Oct 2019 21:34

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