Advances in Nanomaterials Used in Co-Delivery of siRNA and Small Molecule Drugs for Cancer Treatment

Abstract

Recent advancements in nanotechnology have improved our understanding of cancer treatment and allowed the opportunity to develop novel delivery systems for cancer therapy. The biological complexities of cancer and tumour micro-environments have been shown to be highly challenging when treated with a single therapeutic approach. Current co-delivery systems which involve delivering small molecule drugs and short-interfering RNA (siRNA) have demonstrated the potential of effective suppression of tumour growth. It is worth noting that a considerable number of studies have demonstrated the synergistic effect of co-delivery systems combining siRNA and small molecule drugs, with promising results when compared to single-drug approaches. This review focuses on the recent advances in co-delivery of siRNA and small molecule drugs. The co-delivery systems are categorized based on the material classes of drug carriers. We discuss the critical properties of materials that enable co-delivery of two distinct anti-tumour agents with different properties. Key examples of co-delivery of drug/siRNA from the recent literature are highlighted and discussed. We summarize the current and emerging issues in this rapidly changing field of research in biomaterials for cancer treatments.

Keywords: cancer treatment; drug-siRNA co-delivery systems; multifunctional nanocarrier; siRNA delivery.

Figure 1

The structures and size range of vehicles used to co-deliver drug molecules and siRNA (not drawn to scale).

Figure 2

The preparation of folic acid-conjugated mesoporous silica nanoparticles loaded with myricetin and MRP-1 siRNA Note: MRP1 is equivalent to ATP binding cassette subfamily C member 1 (ABCC1). The MRP subfamily of genes is involved in multi-drug resistance. Reprinted from [31].

Figure 3

Illustration of self-assembly at pH 7.4 and intracellular releasing behaviour of amphiphilic block copolymer of monomethoxylpoly(ethylene glycol), poly(l-lysine), and poly(aspartyl(Benzylamine-co-(Diisopropylamino)ethylamine))mPEG-PLLys-PLAsp(BzA-co-DIP), abbreviated as PELABD micelles, for combinatorial delivery of hydrophobic anticancer drugs (Doxorubicin) and siRNA. Reprinted with permission from [46]. Copyright 2020 Springer Nature.

Figure 4

Fabrication of the AuNP-based targeted drug delivery system (TDDS) with an engineered bi-functional recombinant fusion protein TRAF(C) (TR), loaded with doxorubicin and ERBB2-siRNA (Au-TR-DX-si). It was used for further studies in vitro and in vivo. Reprinted with permission from [100]. Copyright Royal Society of Chemistry 2012.