Biomimetic gold nanocomplexes for gene knockdown: Will gold deliver dividends for small interfering RNA nanomedicines?

RNA interference (RNAi) effectors such as small interfering RNA (siRNA) and micro RNA (miRNA) can selectively downregulate any gene implicated in the pathology of a disease. Therefore, RNAi-based therapies have immense potential for the treatment of a wide range of diseases. However, pharmacokinetic and pharmacodynamic studies have revealed that these therapeutic agents have poor bioactivity due to a number of factors, including insufficient plasma drug levels, short plasma half-lives, renal clearance, and hepatic metabolism. Non-viral delivery may facilitate the clinical application of siRNA-based therapeutics by helping to overcome these barriers. Recently, the potential of gold nanoparticles (AuNPs) as multifunctional carriers for transporting drugs, proteins, and genetic materials has been demonstrated. In this review, some of the key properties of AuNPs relevant to siRNA delivery, such as physical properties and surface chemistry have been described. In addition, the ability of AuNP-based formulation strategies to successfully overcome delivery barriers associated with siRNA, and the potential for this material to translate into safe and effective nanomedicines are critically discussed.