Abstract

Ultrasound-Mediated Surface Engineering of Theranostic Magnetic Nanoparticles: An Effective One-Pot Functionalization Process Using Mixed Polymers for siRNA Delivery

Liron L. Israel, Emmanuel Lellouche, Jean-Marc Grenèche, Moshe Bechor, Shulamit Michaeli and Jean-Paul Lellouche

Nano-sized materials have been studied for diverse clinical applications, partly because their size-dependent physical properties and nanometer-scale dimensions have important roles in biological systems. Synergistic combinations of differently nanostructured materials, such as polymer-coated magnetic nanoparticles (NPs), strongly promoted various multifunctional nano-medical platforms for simultaneous diagnosis and therapy in the rapidly emerging area of theranostics. In this context, magnetically responsive Ce cation-doped maghemite (γ-Fe2O3) NPs form a useful NPs basis towards a new type of polycationic polymer/organic species-grafted maghemite NPs for both drug delivery and imaging. The versatility of the Ce cation-doped maghemite NPs fabrication process mediated by high-power ultrasound (US) enables the development of a new one-step time-saving US-driven variant fabrication of corresponding polymer/organic species-grafted NPs. Thus, two types of organic polycationic species, a branched 25 kDa polyethylene imine (b-PEI25) polymer and a generation 2 (G2) PAMAM (poly(amidoamine)) dendrimer biopolymer, were simultaneously used during this US-mediated NPs system fabrication to effectively deliver optimized small interfering RNA (siRNA) applications as a proof of concept. This unique one-step fabrication protocol affords a positively charged magnetic core grafted with mixed organic species nanocomposite particles that enables both gene silencing therapy and magnetic resonance imaging.