Sequential release of nanoparticle payloads from ultrasonically burstable capsules.
In many biomedical contexts ranging from chemotherapy to tissue engineering, it is beneficial to sequentially present bioactive payloads. Explicit control over the timing and dose of these presentations is highly desirable. Here, we present a capsule-based delivery system capable of rapidly releasing multiple payloads in response to ultrasonic signals. In vitro, these alginate capsules exhibited excellent payload retention for up to 1 week when unstimulated and delivered their entire payloads when ultrasonically stimulated for 10-100 s. Shorter exposures (10 s) were required to trigger delivery from capsules embedded in hydrogels placed in a tissue model and did not result in tissue heating or death of encapsulated cells. Different types of capsules were tuned to rupture in response to different ultrasonic stimuli, thus permitting the sequential, on-demand delivery of nanoparticle payloads. As a proof of concept, gold nanoparticles were decorated with bone morphogenetic protein-2 to demonstrate the potential bioactivity of nanoparticle payloads. These nanoparticles were not cytotoxic and induced an osteogenic response in mouse mesenchymal stem cells. This system may enable researchers and physicians to remotely regulate the timing, dose, and sequence of drug delivery on-demand, with a wide range of clinical applications ranging from tissue engineering to cancer treatment.
Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, RI 02881, USA; Department of Chemical Engineering, University of Rhode Island, Kingston, RI 02881, USA.
Stephen
S
Kennedy
Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Jennifer
J
Hu
Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Anatomy, Tissue Engineering Research Group and Advanced Materials and Bioengineering Research Center, Royal College of Surgeons in Ireland, Dublin, Ireland.
Cathal
C
Kearney
Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Hadas
H
Skaat
Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Luo
L
Gu
Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Marco
M
Gentili
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, RI 02912, USA; Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02912, USA.
Herman
H
Vandenburgh
Wyss Institute for Biologically Inspired Engineering, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA. Electronic address: mooneyd@seas.harvard.edu.
David
D
Mooney
D000464:Alginates / Q000737:chemistry; D000818:Animals; D002214:Capsules / Q000737:chemistry*; D002645:Chickens; D020723:Glucuronic Acid / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010012:Osteogenesis; D023822:Tissue Engineering; D014465:Ultrasonics
D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D020100:Hydrogels; D006046:Gold; D020723:Glucuronic Acid
Biomaterials; Controlled release; Drug delivery; Ultrasound response