Polymer-Functionalized Nanodiamond Platforms as Vehicles for Gene Delivery

Abstract

Gene therapy holds great promise for treating diseases ranging from inherited disorders to acquired conditions and cancers. Nonetheless, because a method of gene delivery that is both effective and safe has remained elusive, these successes were limited. Functional nanodiamonds (NDs) are rapidly emerging as promising carriers for next-generation therapeutics with demonstrated potential. Here we introduce NDs as vectors for in vitro gene delivery via surface-immobilization with 800 Da polyethyleneimine (PEI800) and covalent conjugation with amine groups. We designed PEI800-modified NDs exhibiting the high transfection efficiency of high molecular weight PEI (PEI25K), but without the high cytotoxicity inherent to PEI25K. Additionally, we demonstrated that the enhanced delivery properties were exclusively mediated by the hybrid ND-PEI800 material and not exhibited by any of the materials alone. This platform approach represents an efficient avenue toward gene delivery via DNA-functionalized NDs, and serves as a rapid, scalable, and broadly applicable gene therapy strategy.

Nanodrug applications in photodynamic therapy

“…They are biocompatible, have minimal cytotoxicity and are commercially available carbon nanomaterials with a diamond structure at a nanometer scale and offer potential for medical applications. They are suitable for controlled drug delivery due to their capability to slowly and consistently release drugs, have a precise particle distribution, a high surface area to volume ratio and a substantial capacity for drug loading [38,63,64]. Moreover, NDs are stable in water which makes them a promising and important tool, provided their retention time is not too long [64].…”

Lysine-functionalized nanodiamonds as gene carriers: development of stable colloidal dispersion for in vitro cellular uptake studies and siRNA delivery application

“…[16][17][18] In order to synthesize ND-based gene carriers, the aim is to generate a cationic surface, which can electrostatically interact with anionic genetic materials. 19,20 Such examples are noncovalent functionalization with polymers like polyethylenimine 21 and covalent conjugation of derived organic moieties like triethylammonium groups. 22 Introducing protonable biomolecules, including amino acids, peptides, and proteins, on the ND surface is a novel approach for functionalization.…”

Luminescent nanodiamonds for biomedical applications

“…Acid treatments: Hydrogen plasma treatment (Thoms et al 1994;Strother et al 2002;Knickerbocker et al 2003) -Nitric and sulphuric acid (Kong et al 2005a;Huang and Chang 2004;Liu et al 2008;Chao et al 2007;Ushizawa et al 2002) Annealing in hydrogen gas (Härtl et al 2004;Christiaens et al 2006;Saini et al 2008) -Nitric acid Huang et al 2008;Sushchev et al 2008;Mitev et al 2007) Water vapour treatment (Ando et al 1996a) -Hydrochloric acid (Kossovsky et al 1995;Mitev et al 2007) Borane (BH3) (Krüger et al 2006;Neugart et al 2007;Liang et al 2009;Zhang et al 2009b) -Perchloric acid (Xu et al 2005) -Potassium dichromate and sulphuric acid (Mitev et al 2007) -Sulfuric acid and potassium permanganate (Xu et al 2005) Annealing in:…”

“…-apoobelin ) -aflatoxin B1 (AfB1) ) -DNA (Fu et al 2007) -luciferase Puzyr' et al 2004) -Alpha-bungarotoxin (Liu et al 2008 (Miller and Brown 1996;Knickerbocker et al 2003;Lu et al 2004;Strother et al 2002;Yang et al 2002;Takahashi et al 2003;Yeap et al 2008;Zhang et al 2009b;Zheng et al 2009;Chang et al 2010) (Strother et al 2002;Takahashi et al 2003;Ida et al 2003;Tsubota et al 2003;Härtl et al 2004;Christiaens et al 2006;Chang et al 2010) (Liu et al 2004;Ando et al 1996b;Khabashesku et al 2005;Ando et al 1996a;Ando et al 1993) (Ando et al 1996a;Ikeda et al 1998;Takahashi et al 2003;Miller and Brown 1996) Silanes Aryl Alkyl Amino (Zhang et al 2009b;Liang et al 2009;Krüger et al 2006;Yeap et al 2008 Zheng et al 2009) choice of biological buffer systems or media is also important, since both foetal bovine serum and phosphate buffered saline, two common biological buffer systems, tend to cause re-aggregation (Neugart et al 2007;Vaijayanthimala et al 2009). Despite the challenges involved in preparing and maintaining de-aggregated nanodiamonds, positive results strongly support their use in biological applications.…”

“…The targeted delivery of therapeutic DNA (Zhang et al 2009b) or cytotoxic drugs could maximise the efficacy of therapy as well as minimise the side effects and/or collateral damage to normal tissue in vivo. Nanodiamonds can potentially provide a delivery vehicle for these treatments.…”