Enhanced siRNA Delivery and Selective Apoptosis Induction in H1299 Cancer Cells by Layer-by-Layer-Assembled Se Nanocomplexes: Toward More Efficient Cancer Therapy

Abstract

Nanotechnology has made an important contribution to oncology in recent years, especially for drug delivery. While many different nano-delivery systems have been suggested for cancer therapy, selenium nanoparticles (SeNPs) are particularly promising anticancer drug carriers as their core material offers interesting synergistic effects to cancer cells. Se compounds can exert cytotoxic effects by acting as pro-oxidants that alter cellular redox homeostasis, eventually leading to apoptosis induction in many kinds of cancer cells. Herein, we report on the design and synthesis of novel layer-by-layer Se-based nanocomplexes (LBL-Se-NCs) as carriers of small interfering RNA (siRNA) for combined gene silencing and apoptosis induction in cancer cells. The LBL-Se-NCs were prepared using a straightforward electrostatic assembly of siRNA and chitosan (CS) on the solid core of the SeNP. In this study, we started by investigating the colloidal stability and protection of the complexed siRNA. The results show that CS not only functioned as an anchoring layer for siRNA, but also provided colloidal stability for at least 20 days in different media when CS was applied as a third layer. The release study revealed that siRNA remained better associated with LBL-Se-NCs, with only a release of 35% after 7 days, as compared to CS-NCs with a siRNA release of 100% after 48 h, making the LBL nanocarrier an excellent candidate as an off-the-shelf formulation. When applied to H1299 cells, it was found that they can selectively induce around 32% apoptosis, while significantly less apoptosis (5.6%) was induced in NIH/3T3 normal cells. At the same time, they were capable of efficiently inducing siRNA downregulation (35%) without loss of activity 7 days post-synthesis. We conclude that LBL-Se-NCs are promising siRNA carriers with enhanced stability and with a dual mode of action against cancer cells.

Chitosan coated metallic nanoparticles with stability, antioxidant, and antibacterial properties: Potential for wound healing application

“…This observation may have ensued due to the use of dried samples to carry the TEM analysis, whereas in the DLS the hydrodynamic size of NPs is was measured instead. This is while the TEM image of CSNPs (Figure 2(j)) like our previous report is presented with an undefined shape having heterogeneous morphology 50 …”

Therapeutic Potential and Main Methods of Obtaining Selenium Nanoparticles

“…One of the reasons for the toxicity of Se for cancer cells as compared to normal somatic cells is the more reducing environment of cancer cells, which stimulates the formation of Se–S adducts from Se compounds [ 142 ]. Such Se–S adducts can mimic cystine and mixed disulfides, causing enhanced receptor-mediated uptake of Se by cancer cells [ 142 , 143 , 144 , 145 , 146 ].…”

“…It was found that LBL-Se-NC is able to selectively induce apoptosis in 32% of human non-small cell lung carcinoma (H1299 cells), which is 5.7 times more than in normal NIH3T3 cells (mouse embryonic fibroblasts). When cancer cells were treated with the CS-NC complex in the same concentration range, there was no clear difference in the viability of these cells compared to normal cells, which indicated the selective and effective induction of apoptosis by LBL-Se-NC nanoparticles [ 146 , 166 ].…”

A Lipid-Coated Nanoconstruct Composed of Gold Nanoparticles Noncovalently Coated with Small Interfering RNA: Preparation, Purification and Characterization

“…A distinct field of research and development of these systems is the use of solid (metal) nanoparticles enclosed in a shell and serving as a carrier of a nucleic acid. For instance, there are reports on the efficient delivery of small interfering RNA (siRNA) via gold nanoparticles (AuNPs) [9] and selenium nanoparticles [10] coated with chitosan and gold nanorods covered with two layers of polyelectrolytes [11].…”

“…Our study was aimed at creating multilayer nanoconstructs (MLNCs) based on spherical AuNPs on whose surface an siRNA layer is adsorbed and surrounded by a lipid (siRNA) via gold nanoparticles (AuNPs) [9] and selenium nanoparticles [10] coated with chitosan and gold nanorods covered with two layers of polyelectrolytes [11].…”