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. Chitosandeoxycholic acid nanoparticles containing perfluoropentane and iron oxide (d 0 = 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 peakto-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.

Novel method for the formation of monodisperse superheated perfluorocarbon nanodroplets as activatable ultrasound contrast agents

“…Over the past two decades, researchers have evaluated the potential of converting nanoscale droplets of liquid PFC emulsion into gas-phase MBs for diagnostic and potential therapeutic uses, 5–13 image-guided and high-intensity focused ultrasound (HIFU) therapy, 14–19 drug or gene delivery, 20–25 sonoporation 26 and DNA fragmentation. 27 This conversion induced by exposure to US, is referred to as acoustic droplet vaporization (ADV), 28,29 with such US contrast agent referred to a phase-change contrast agent (PCCA).…”

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

“…To this hybrid system, siRNA was electrostatistically loaded and delivered to lung and breast cancer cell lines. The results demonstrated enhanced delivery and effect of siRNA in the recipient cells upon ultrasound exposure (Lee et al, 2017). …”

Theranostic Nanoparticles for Tracking and Monitoring Disease State

“…36 The nano-droplets’ core consists of liquid perfluoropentane and magnetic nanoparticles with a shell comprising chitosan-deoxycholic acid conjugates and siRNA, totaling a size of ~257 nm. After exposure to ultra-sound, the liquid droplets undergo phase transition to form gas microbubbles on the sizes of 3822 nm.…”

“…During the ultrasound exposure period, acoustic imaging was also used to estimate the acoustic power of cavitation emissions and monitor the correlation between the energy of these acoustic emissions from the microbubbles and the treatment efficacy. 36 …”