Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer—The Case for Combined Delivery?

Abstract

Gene therapy arises as a great promise for cancer therapeutics due to its potential to silence genes involved in tumor development. In fact, there are some pivotal gene drivers that suffer critical alterations leading to cell transformation and ultimately to tumor growth. In this vein, gene silencing has been proposed as an active tool to selectively silence these molecular triggers of cancer, thus improving treatment. However, naked nucleic acid (DNA/RNA) sequences are reported to have a short lifetime in the body, promptly degraded by circulating enzymes, which in turn speed up elimination and decrease the therapeutic potential of these drugs. The use of nanoparticles for the effective delivery of these silencers to the specific target locations has allowed researchers to overcome this issue. Particularly, gold nanoparticles (AuNPs) have been used as attractive vehicles for the target-specific delivery of gene-silencing moieties, alone or in combination with other drugs. We shall discuss current trends in AuNP-based delivery of gene-silencing tools, considering the promising road ahead without overlooking existing concerns for their translation to clinics.

Gene Therapy in Cancer Treatment: Why Go Nano?

“…Delivery of TNAs, such as genes, oligonucleotides, miRNAs or siRNAs to cancer cells has allowed to tackle cancer via the silencing oncogenes or restoring the expression of tumor suppressor genes [8][9][10][11][12][13][14][15][16][17][18][19]. Most of these approaches (e.g., antisense therapy, RNA interference (RNAi), gene editing) aim at gene alteration/modulation [16][17][18][19][76][77][78][79][80][81] -see Figure 3. The immunization gene therapies, particularly chimeric antigen receptor (CAR) in T cells (CAR-T cells) based therapies, stand-out since they represent the higher number of therapeutic strategies in clinical practice.…”

“…The mounting knowledge on the characteristics of tumor cells and surrounding TME have sparked the use of gene therapy to tackle cancer molecular mechanisms. Gene therapy consists of the introduction of exogenous nucleic acids, such as genes, gene segments, oligonucleotides, miRNAs or siRNAs into cells envisaging a target gene edition, expression modulation of a target gene, mRNA or synthesis of an exogenous protein [8][9][10][11][12][13][14][15][16][17][18][19]. Gene transfer into tumor cells has been demonstrated via administration of therapeutic nucleic acids (TNAs) ex vivo and/or in vivo (Figure 1) [20].…”

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

“…These nanoparticles are generally modified with polymers or PEG-containing linkers to conjugate or complex with drug or siRNA/DNA. Hence, they are increasingly being used for drug or gene delivery purposes by exploiting the advantages of increased drug/gene loading, low toxicity due to the inert nature of gold, efficiency in cell uptake, fast endosomal escape, and stability in the circulation (Mendes, Fernandes, & Baptista, 2017). …”

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics

“…A cationic solid lipid nanoparticle also showed effective inhibition of HCC growth by delivering shRNA for the NURP gene [137], and similarly, siRNA to PLK1 gene delivered by chitosan nanoparticles efficiently suppressed HCC cell growth both in vitro and in vivo [138]. Gold nanoparticles, which have been used as attractive chemical vehicles for the gene delivery [139], and are currently used for gene editing [140], have also been tested for their applicability in HCC gene therapy in vivo, owing to their ability to modify the surface to attach multiple ligands, their superior visibility, and their low cytotoxicity [141].…”