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In Situ Transfection by Controlled Release of Lipoplexes Using Acoustic Droplet Vaporization
Author(s) -
Juliar Benjamin A.,
Bromley Melissa M.,
Moncion Alexander,
Jones Denise C.,
O'Neill Eric G.,
Wilson Christopher G.,
Franceschi Renny T.,
Fabiilli Mario L.
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201600008
Subject(s) - transfection , biophysics , emulsion , chemistry , gene delivery , nucleic acid , fluorescein , sonoporation , vaporization , viability assay , microbiology and biotechnology , fluorescence , in vitro , ultrasound , biochemistry , gene , biology , microbubbles , optics , physics , organic chemistry , acoustics
Localized delivery of nucleic acids to target sites (e.g., diseased tissue) is critical for safe and efficacious gene therapy. An ultrasound‐based technique termed acoustic droplet vaporization (ADV) has been used to spatiotemporally control the release of therapeutic small molecules and proteins contained within sonosensitive emulsions. Here, ADV is used to control the release of lipoplex—containing plasmid DNA encoding an enhanced green fluorescent protein reporter—from a sonosensitive emulsion. Focused ultrasound (3.5 MHz, mechanical index (MI) ≥ 1.5) generates robust release of fluorescein (i.e., surrogate payload) and lipoplex from the emulsion. In situ release of the lipoplex from the emulsion using ADV (MI = 1.5, 30 cycles) yields a 55% release efficiency, resulting in 43% transfection efficiency and 95% viability with C3H/10T1/2 cells. Without exposure to ultrasound, the release and transfection efficiencies are 5% and 7%, respectively, with 99% viability. Lipoplex released by ADV retains its bioactivity while the ADV process does not yield any measureable sonoporative enhancement of transfection. Co‐encapsulation of Ficoll PM 400 within the lipoplex‐loaded emulsion, and its subsequent release using ADV, yield higher transfection efficiency than the lipoplex alone. The results demonstrate that ADV can have utility in the spatiotemporal control of gene delivery.