Abstract
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.
Highlights
Nano-sized materials are currently designed and fabricated for a wide range of diverse clinical applications
The corresponding CAN-maghemite NPs aqueous suspension arising from the CAN-mediated high-power ultrasonication of former Massart magnetite NPs (20 mL, Sonics®, Vibracell, 750 Watt, power modulator set-up at 25%, Titanium horn, 45 min irradiation, 0°C, dry inert Ar atmosphere) was added at t=45 min to two types of reagent mixtures: 10.0 mg of b-PEI25 (0.00032 mmol, 10 mg/mL ddH2O solution) and 10.0 mg of generation 2 (G2) PAMAM dendrimer (0.00307 mmol, 0.058 mL of a 20% in MeOH solution, in 0.5 mL ddH2O) species via a one-shot mixture injection into the US reaction medium
The resulting hydrophilic highly stable browncolored injPEI25/PAMAMG2-CAN-γ-Fe2O3 NPs were washed with ddH2O (3 x 10 mL) using an Amicon® Ultra-15 centrifugal filter device (100 K) operated at 4,000 rpm for 5 min
Summary
Nano-sized materials are currently designed and fabricated for a wide range of diverse clinical applications. Selected small functional iron oxide NPs (in the size range of 5-30 nm) are commercially available and FDA-approved [6] for clinical use (mainly MRI) In this context, numerous in vitro toxicity studies concerning different iron oxide particles functionalized by a great variety of polymers [7,8] such as polyethylene imine (PEI) [9] PVA (polyvinyl alcohol), PLL (poly-L-lysine), PDMA (poly N,Ndimethylacrylamide) and PEGs (polyethylene glycols) [10] have recently been reviewed, showing the major importance of correctly designed NPs surface engineering. This strong mono-electronic CAN oxidant enabled an easy oxidation of the starting Fe3O4 phase together with a controlled Ce cation/complex NPs surface doping, resulting in an effective NPs aggregation control (high positive charge repulsion) and coordinative attachment (Ce cation/complex ligand exchange) of any Lewis base-behaving organic species [11]
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