Gold Nanoparticles for Vectorization of Nucleic Acids for Cancer Therapeutics

Abstract

Cancer remains a complex medical challenge and one of the leading causes of death worldwide. Nanomedicines have been proposed as innovative platforms to tackle these complex diseases, where the combination of several treatment strategies might enhance therapy success. Among these nanomedicines, nanoparticle mediated delivery of nucleic acids has been put forward as key instrument to modulate gene expression, be it targeted gene silencing, interference RNA mechanisms and/or gene edition. These novel delivery systems have strongly relied on nanoparticles and, in particular, gold nanoparticles (AuNPs) have paved the way for efficient delivery systems due to the possibility to fine-tune their size, shape and surface properties, coupled to the ease of functionalization with different biomolecules. Herein, we shall address the different molecular tools for modulation of expression of oncogenes and tumor suppressor genes and discuss the state-of-the-art of AuNP functionalization for nucleic acid delivery both in vitro and in vivo models. Furthermore, we shall highlight the clinical applications of these spherical AuNP based conjugates for gene delivery, current challenges, and future perspectives in nanomedicine.

Engineering Gold Nanostructures for Cancer Treatment: Spherical Nanoparticles, Nanorods, and Atomically Precise Nanoclusters

“…Spherical Au nanoparticles have been widely utilized in cancer treatment, mainly thanks to their unique physicochemical properties, their excellent biocompatibility, and particularly their characteristic surface plasmon resonance absorbance with specific wavelengths [ 19 , 20 ]. Spherical Au nanoparticles can be applied for cancer treatment in several ways such as photothermal therapy, radiotherapy, tumor imaging, and serving as drug delivery systems [ 21 , 22 , 23 , 24 , 25 , 26 ].…”

“…In addition, spherical Au nanoparticles have been attracting considerable interest as non-toxic drug carrier systems for cancer treatment, thanks to the large surface-to-volume ratio; easy tuning of surface charge, hydrophilicity, and functionality; and outstanding stability [ 37 , 38 , 39 ]. Various biocompatible polymers (e.g., polyethylene glycol (PEG) [ 40 ], polyelectrolyte [ 37 ], DNA [ 25 ], liposome [ 41 ], and other bio-macromolecules [ 42 ]) can be used to tune the tumor microenvironment [ 43 ] and, more importantly, enhance the stability, payload capacity, and the cellular uptake. Muhammad et al reported that the PEG-capped AuNPs can enable efficient delivery of anti-cancer therapeutics of bleomycin and doxorubicin into HeLa cells while maintaining drug cytotoxicity [ 40 ].…”

Recent Advances in the Development of Exogenous dsRNA for the Induction of RNA Interference in Cancer Therapy

“…Tunability in size and surface characteristics makes them promising candidates as drug delivery vehicles. Moreover, there is an opportunity for a very precise control over the size, shape, and surface properties of such gold nanoparticles and of their functionalization using various biomolecules [ 47 ]. For example, oligopeptides have been used to develop siRNA-delivery systems for the treatment of glioblastomas and breast cancer [ 48 , 49 ].…”

Next-generation engineered nanogold for multimodal cancer therapy and imaging: a clinical perspectives

“…This generates a need for delivery systems to deliver nucleic acids that protect them from physiological conditions. Due to the unique properties and biocompatibility, AuNPs are used to deliver nucleic acids to the target cells without any transfection agent [ 166 ]. Moreover, cationic AuNPs can form electrostatic complexes with nucleic acids, rendering nuclease protection to nucleic acids and efficiently delivering it to target cells [ 167 ].…”