Graphene materials as 2D non-viral gene transfer vector platforms

Abstract

Advances in genomics and gene therapy could offer solutions to many diseases that remain incurable today, however one of the critical reasons halting clinical progress is due to the difficulty in designing efficient and safe delivery vectors for the appropriate genetic cargo. Safety and largescale production concerns counter-balance the high gene transfer efficiency achieved with viral vectors, while non-viral strategies have yet to become sufficiently efficient. The extraordinary physicochemical, optical and photothermal properties of graphene-based materials (GBMs) could offer two-dimensional (2D) components for the design of nucleic acid carrier systems. We discuss here such properties and their implications for the optimization of gene delivery. While the design of such vectors is still in its infancy, we provide here an exhaustive and up-to-date analysis of the studies that have explored GBMs as gene transfer vectors, focusing on the functionalization strategies followed to improve vector performance and on the biological effects attained.

Graphene Oxide as 2D Platform for Complexation and Intracellular Delivery of siRNA

“…These findings suggest opportunities to utilize GO as an intracellular nanocarrier of double-stranded oligonucleotides which can be used in applications other than biosensing, including gene silencing and forced expression of specific gene products. In fact, GO has already been used in a number of studies to load and deliver double-stranded plasmid DNA and siRNA, albeit always as a component of more complex delivery systems 9 . As such, GO had no direct interaction with the nucleic acid but provided a scaffold for cationic moietiessuch as positively charged polymers 10 , dendrimers 32 , polysaccharides 11 and peptides 12 that complexed negatively charged oligonucleotides through electrostatic interactions.…”

“…This is especially relevant when the oligonucleotide of choice is double stranded, since hydrophobic and π-π interactions between the nucleobases and the GO lattice are sterically hindered 6 . A number of studies (reviewed elsewhere 9 ) have used GO to complex and deliver double-stranded nucleic acids intracellularly, including plasmid DNA (pDNA) and small interfering RNA (siRNA). However, all of them relied on functionalization of the material with positively charged moietiesincluding cationic polymers 10 , polysaccharides 11 and cell penetrating peptides 12 which have previously been used as delivery vectors on their own, but whose biocompatibility is far from ideal.…”

Graphene-Based Nanomaterials for Theranostic Applications

“…48 Small size, high surface area to mass ratio, easy surface functionalization, ability to load and condense nucleic acids even in the absence of cationic groups throughinteractions, protection of nucleic acids from endonuclease digestion, high cellular uptake and low toxicity has made graphene and its derivatives a suitable candidate for gene delivery. 5 The ease of functionalization of these materials with cationic polymers and targeting moieties to improve their biocompatibility, nucleic acid loading e±ciency and overall therapeutic e±cacy is due to the presence of numerous oxygen containing functional groups on the surface of these materials that allow for easy conjugation and derivatization.…”

“…5,8 Covalent and non-covalent functionalization of GO and rGO nanosheets with cationic polymers like polyethylenimine (PEI), polysaccharides like chitosan and dendrimers such as polyamidoamine (PAMAM) have been carried out to develop nanoconstructs with improved nucleic acid binding e±ciency and physiological stability for achieving better transfection and therapeutic outcomes. 8,48 The cationic molecules provide a net positive charge on the surface of the nanoconstructs that help in improving the nucleic acid condensation e±ciency through electrostatic interactions. Incorporation of PEG alongwith these groups have also shown to improve the aqueous stability and biocompatibility of these nanoconstructs.…”

Dynamic interactions and intracellular fate of label-free, thin graphene oxide sheets within mammalian cells: role of lateral sheet size

“…Graphene oxide (GO), the oxidized form of graphene, has been one of the most researched 2-dimensional (2D) materials in nanomedicine due to its advantageous intrinsic properties [1][2][3] . For example, GO has a large surface-areatovolume ratio allowing high capacity for loading of cargos via both covalent and non-covalent interactions, while the different (carboxyl, epoxy and hydroxyl) functional groups offer chemical routes/anchor sites for further functionalization.…”