title: Ultrasound-Enhanced siRNA Delivery Using Magnetic Nanoparticle-Loaded Chitosan-Deoxycholic Acid Nanodroplets.
abstract: Small interfering RNA (siRNA) has significant therapeutic potential but its clinical translation has been severely inhibited by a lack of effective delivery strategies. Previous work has demonstrated that perfluorocarbon nanodroplets loaded with magnetic nanoparticles can facilitate the intracellular delivery of a conventional chemotherapeutic drug. The aim of this study is to determine whether a similar agent can provide a means of delivering siRNA, enabling efficient transfection without degradation of the molecule. Chitosan-deoxycholic acid nanoparticles containing perfluoropentane and iron oxide (d0= 7.5 ± 0.35 nm) with a mean hydrodynamic diameter of 257.6 ± 10.9 nm are produced. siRNA (AllStars Hs cell death siRNA) is electrostatically bound to the particle surface and delivery to lung cancer cells and breast cancer cells is investigated with and without ultrasound exposure (500 kHz, 1 MPa peak-to-peak focal pressure, 40 cycles per burst, 1 kHz pulse repetition frequency, 10 s duration). The results show that siRNA functionality is not impaired by the treatment protocol and that the nanodroplets are able to successfully promote siRNA uptake, leading to significant apoptosis (52.4%) 72 h after ultrasound treatment.
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Old Road, Campus, OX3 7DQ, UK.
authors.forename: Jeong Yu
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Old Road, Campus, OX3 7DQ, UK.
authors.forename: Calum
authors.initials: C
authors.lastname: Crake
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Old Road, Campus, OX3 7DQ, UK.
authors.forename: Boon
authors.initials: B
authors.lastname: Teo
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Old Road, Campus, OX3 7DQ, UK.|Faculty of Engineering and the Environment, Southampton University, Southampton, SO17 1BJ, UK.
authors.forename: Dario
authors.initials: D
authors.lastname: Carugo
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Old Road, Campus, OX3 7DQ, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: de Saint Victor
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Old Road, Campus, OX3 7DQ, UK.
authors.forename: Anjali
authors.initials: A
authors.lastname: Seth
authors.affiliation: Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, Old Road, Campus, OX3 7DQ, UK.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Stride
mesh_terms: D000072283:A549 Cells; D048271:Chitosan / Q000737:chemistry*; D003840:Deoxycholic Acid / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D061986:MCF-7 Cells; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology
chemical_list: D058185:Magnetite Nanoparticles; D034741:RNA, Small Interfering; D003840:Deoxycholic Acid; D048271:Chitosan
keywords: cancer therapy; microbubbles; nanodroplets; siRNA; ultrasound