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.
Highlights
Nanotechnology has made important contributions to oncology in recent years, thanks to its uniquely appealing features for drug delivery, diagnosis, and imaging (Pucci et al, 2019)
The hydrodynamic size as measured by dynamic light scattering (DLS) being larger than what is measured by Transmission electron microscopy (TEM) is likely due to the fact that in DLS, the polymer coating of the particle is fully hydrated, while the samples are dehydrated for TEM imaging
The peak located at 1,150 cm−1 is the result of chitosan deacetylation and is related to asymmetric small interfering RNA (siRNA) Delivery and Selective Apoptosis Induction vibrations of CO in the oxygen bridge
Summary
Nanotechnology has made important contributions to oncology in recent years, thanks to its uniquely appealing features for drug delivery, diagnosis, and imaging (Pucci et al, 2019). The use of nanoparticles as drug delivery systems has the potential to overcome some severe adverse effects induced by conventional chemotherapeutic drugs on normal cells. Scientists have been able to control the architecture of nanocarriers in such a way that they can promote local delivery (targeting) and even controlled drug release (Fritz and Lenardo, 2019; Martinelli et al, 2019). According to their design, nanocarriers have the capability of packaging and protecting cargos that are toxic, fragile, insoluble, or unstable for delivery as free drugs (Saw and Song, 2020). Se–S adducts could simulate cystine and mixed disulfides, causing enhanced receptor-mediated uptake of Se in cancer cells (Banjac et al, 2008; Olm et al, 2009; Mandal et al, 2010; Ikram et al, 2021)
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