Approach to Rapid Synthesis and Functionalization of Iron Oxide Nanoparticles for High Gene Transfection

Abstract

Surface functionalization of theranostic nanoparticles (NPs) typically relies on lengthy, aqueous post-synthesis labeling chemistries that have limited ability to fine tune surface properties and can lead to NP heterogeneity. The need for a rapid, simple synthesis approach that can provide great control over the display of functional moieties on NP surfaces has led to increased use of highly selective bioorthoganol chemistries including metal-affinity coordination. Here we report a simple approach for rapid production of a superparamagnetic iron oxide NPs (SPIONs) with tunable functionality and high reproducibility under aqueous conditions. We utilize the high affinity complex formed between catechol and Fe(III) as a means to dock well-defined catechol modified polymer modules on the surface of SPIONs during sonochemical co-precipitation synthesis. Polymer modules consisted of chitosan and poly(ethylene glycol) (PEG) copolymer (CP) modified with catechol (CCP), and CCP functionalized with cationic polyethylenimine (CCP-PEI) to facilitate binding and delivery of DNA for gene therapy. This rapid synthesis/functionalization approach provided excellent control over the extent of PEI labeling, improved SPION magnetic resonance imaging (MRI) contrast enhancement and produced an efficient transfection agent.

Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

“…Modification of the surface of Fe 3 O 4 NPs with hydrophilic natural polymers such as chitosan (CS), starch, or dextran, or synthetic polymers such as polyethylene glycol, polyethylene phthalate, polyvinyl pyrrolidone, or other distinctive polymers was done to reduce the oxidation, agglomeration, and toxicity and provide multifunction treatments [ 28 , 32 ]. These kinds of composites can effectively deliver therapeutic molecules to target sites and then achieve targeted drug/gene delivery.…”

“…When employing Fe 3 O 4 NPs as gene transfers, they are usually coated with organic ligands, such as PEG, PEI, aminosilanes, chitosan, or polyamidoamine (PAMAM) dendrimer [ 32 , 117 ]. The gene would be linked on the carrier typically through electrostatic interactions between gene and polymer; gold coating and lipid membrane could also support anchorage points for genes to be connected.…”

“…Zhang et al displayed Fe 3 O 4 NP magnetofection carrier for enhanced transfection of red fluorescent protein encoding plasmid DNA, which applied polymer modules comprising chitosan and PEG copolymer (CP) modified with catechol (CCP). CCP was coated on the surface of Fe 3 O 4 NPs (IOCCP), and PEI was further modified with CCP (IOCCP-PEI) for the binding of DNA [ 32 ]. Significantly, DNA-loaded IOCCP-PEI had outstanding transfection effect in vitro, and further functionalization with PEG (IOCCP-PEI-PEG) greatly decreased cytotoxicity without obviously hampering the transfection effect.…”

“…Additionally, naked Fe 3 O 4 NPs have high chemical activity on their surface but are highly prone to oxidization in air, which can lead to significant reduction of their magnetism and dispersibility. Therefore, it is important to consider the functionalization of Fe 3 O 4 NPs with diverse thin and thick materials, such as all kinds of polymers [ 25 , 28 , 29 , 30 , 31 , 32 ], graphene oxide materials [ 33 , 34 , 35 ], silica [ 21 , 36 ], carbon materials [ 37 , 38 ], metal oxide microwave-absorbing materials [ 39 ], and various luminescent materials [ 21 , 40 ]. The modified coatings improve the stability and dispersibility of naked Fe 3 O 4 NPs and provide chemical coordination/conjugation sites for drugs, targeted ligands, genes, and other therapeutic reagents that can optimize the biomedical utilization of targeted drug/gene delivery.…”

Polymer functionalized gold nanoparticles as nonviral gene delivery reagents

“…The conjugation of PEI to nanoparticles favors DNA sedimentation and cellular uptake and enhances the transfection efficiency . In this regard, Stephen et al . have recently reported the use of chitosan‐PEG grafted with catechol functionalized with cationic PEI on the surface of magnetic nanoparticles.…”