Enhanced delivery of PEAL nanoparticles with ultrasound targeted microbubble destruction mediated siRNA transfection in human MCF-7/S and MCF-7/ADR cells in vitro

Abstract

The gene knockdown activity of small interfering RNA (siRNA) has led to their use as potential therapeutics for a variety of diseases. However, successful gene therapy requires safe and efficient delivery systems. In this study, we choose mPEG-PLGA-PLL nanoparticles (PEAL NPs) with ultrasound targeted microbubble destruction (UTMD) to efficiently deliver siRNA into cells. An emulsification-solvent evaporation method was used to prepare siRNA-loaded PEAL NPs. The NPs possessed an average size of 132.6±10.3 nm (n=5), with a uniform spherical shape, and had an encapsulation efficiency (EE) of more than 98%. As demonstrated by MTT assay, neither PEAL NPs nor siRNA-loaded PEAL NPs showed cytotoxicity even at high concentrations. The results of cellular uptake showed, with the assistance of UTMD, the siRNA-loaded PEAL NPs can be effectively internalized and can subsequently release siRNA in cells. Taken together, PEAL NPs with UTMD may be highly promising for siRNA delivery, making it possible to fully exploit the potential of siRNA-based therapeutics.

Ultrasound-guided therapeutic modulation of hepatocellular carcinoma using complementary microRNAs

“…However, due to the size of PLGA-NP, usually ranging between 100 and 150 nm [23], intravenous administration results in minimal tumor tissue penetration as delivery depends on the enhanced permeability and retention (EPR) effect [24] that is often weak in human tumors [25–27]. Using therapeutic ultrasound, PLGA-NP can be actively delivered into cancer using image-guidance, overcoming the limitations of passive tumor accumulation and delivering miRNA deeply into tumors, even in less vascularized portions of the tumor [28,29]. Through a process termed “sonoporation,” local perforations can be formed on vessel walls, facilitating the delivery of therapeutic agents into cancer [30–32,55–57].…”