Naked DNA, usually in plasmid form, is the simplest form of non-viral transferring of a gene into a target cell [13–16]. Because of low transferring efficiency of a bare plasmid, several physical (electroporation, ultrasound, gas-filled micro-bubbles) and chemical (liposomes) approaches have been exploited to enhance their transformation efficiency [17]. In another type of classification, non-viral delivery vectors can be categorized as organic (lipid complexes, conjugated

polymers, cationic polymers, etc.) and inorganic (magnetic nanoparticles, quantum dots, carbon nanotubes, gold nanoparticles, etc.) systems [18]. Among the materials used to design non-viral vectors, attention has recently increased on the natural GSK2126458 in vivo biomaterials due to their unique properties such as biodegradability, biocompatibility, and controlled release. The delivery carriers necessitate being small enough to be internalized into the cells

and enter the nucleus passing through the cytoplasm and escaping the endosome/lysosome process following endocytosis (Figure 1). The use of nanoparticles in gene delivery can provide both the targeted and sustained gene delivery by protecting the gene against nuclease degradation and improving its stability [19–22]. Figure 1 Internalization of non-viral vectors into cell and passage to nucleus through cytoplasm following endocytosis. Nanoparticles in gene delivery In the field of nanomedicine, selleck kinase inhibitor nanotechnology methods focus on formulating therapeutic biocompatible agents such as nanoparticles, nanocapsules, micellar systems, and conjugates [22, 23]. Nanoparticles are solid and spherical structures ranging to around 100 nm in size and prepared from from natural or synthetic polymers [24]. To reach the large-size nucleic acid molecule, the cytoplasm, or even the

nucleus, a suitable carrier system is required to deliver genes to cells which enhance cell internalization and protect the DNA molecule from nuclease enzymatic degradation (e.g., virosomes, cationic liposomes, and nanoparticles). To achieve the suitable carrier system, the nanoparticles can be considered as a good candidate for therapeutic applications because of several following reasons: (1) They exist in the same size domain as proteins,(2) they have large surface areas and ability to bind to a large number of surface functional groups, and (3) they possess controllable absorption and release properties and particle size and surface characteristics [25]. Nanoparticles can also be coated with molecules to produce a hydrophilic layer at the surface (PEGylation) to increases their blood circulation half-life. Poloxamer, poloxamines, and chitosan have also been studied for surface modifications.