A new formulation of volatile nanodroplets stabilized by a protein and polymer coating and loaded with magnetic nanoparticles is developed. The droplets show enhanced stability and phase conversion efficiency upon ultrasound exposure compared with existing formulations. Magnetic targeting, encapsulation, and release of an anticancer drug are demonstrated in vitro with a 40% improvement in cytotoxicity compared with free drug.

Here, we report quantum dot-incorporating solid lipid nanoparticles (SLNs) for anticancer theranostics with synergistic therapeutic effects of paclitaxel-siRNA combination. The natural components of a low-density lipoprotein (LDL) are reconstituted to produce LDL-mimetic SLNs having a stable core/shell nanostructure incorporating quantum dots and paclitaxel within the lipid shell while anionic siRNA molecules are electrostatically complexed with the outer surface of SLNs. The produced SLN/siRNA complexes efficiently deliver both of paclitaxel and Bcl-2 targeted siRNA into human lung carcinoma cells and exhibit synergistic anticancer activities by triggering caspase-mediated apoptosis as determined by median effect plot analysis. Moreover, the strong fluorescence from quantum dots within SLNs enables in situ visualization of intracellular translocation of SLNs into cancer cells. Our study suggests that LDL-mimetic SLNs can be utilized as a multifunctional and optically traceable nanocarrier for efficient anticancer theranostics.

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.

No abstract

Ultrasound (US), in combination with microbubbles, has been found to be a potential alternative to viral therapies for transfecting biological cells. The translation of this technique to the clinical environment, however, requires robust and systematic optimization of the acoustic parameters needed to achieve a desired therapeutic effect. Currently, a variety of different devices have been developed to transfect cells in vitro, resulting in a lack of standardized experimental conditions and difficulty in comparing results from different laboratories. To overcome this limitation, we propose an easy-to-fabricate and cost-effective device for application in US-mediated delivery of therapeutic compounds. It comprises a commercially available cell culture dish coupled with a silicon-based "lid" developed in-house that enables the device to be immersed in a water bath for US exposure. Described here are the design of the device, characterization of the sound field and fluid dynamics inside the chamber and an example protocol for a therapeutic delivery experiment.