Improved delivery of Mcl-1 and survivin siRNA combination in breast cancer cells with additive siRNA complexes

Abstract

This study aimed at investigating the in uence of commercial transfection reagents (Prime-Fect, Leu-Fect A, and Leu-Fect C) complexed with different siRNAs (CDC20, HSP90, Mcl-1 and Survivin) in MDA-MB-436 breast cancer cells and the impact of incorporating an anionic additive, Trans-Booster, for improving in vitro gene silencing and delivery e ciency. Gene silencing was quantitatively analyzed by real-time RT-PCR while cell proliferation and siRNA uptake were evaluated by the MTT assay and ow cytometry, respectively. Amongst the investigated siRNAs and transfection reagents, Mcl-1/Prime-Fect complexes showed the highest inhibition of cell viability and most effective siRNA delivery. The effect of various formulations on transfection e ciency showed that a anionic additive with 1:1 ratio with siRNA was optimal achieving the lowest cell viability compared to untreated cells and negative control siRNA treatment (p<0.05). Furthermore, the combination of Mcl-1 and survivin siRNA suppressed the growth of MDA-MB-436 cells more effectively than treatment with the single siRNAs and resulted in a cell viability as low as ~20% (vs. non-treated cells). This aligned well with the induction of apoptosis as analyzed by ow cytometry, which revealed higher apoptotic cells with the combination treatment group. We conclude that commercial transfection reagents formulated with Mcl-1/Survivin siRNA combination could serve as a potent anti-proliferation agent in treatment of breast cancers.

Harnessing graphene oxide nanocarriers for siRNA delivery in a 3D spheroid model of lung cancer

“…This analysis demonstrated that upon increasing the CD47_siRNA : GO ratio, it is possible to obtain a higher transfection efficiency, as observed in other studies. 15,68,69 GO thus proves to be a potentially viable alternative to chemically modified GO. This alternative might be preferable in some cases because unmodified GO, such as sGO, is less processed and therefore less expensive and complex.…”

Safe and Effective Delivery of mRNA Using Modified PEI-Based Lipopolymers

“…Therefore, in this study, we explored several cationic lipopolymers of PEI for modRNA delivery. The lipopolymers were previously commercialized for delivery of other nucleic acids such as siRNA [ 49 ] and pDNA [ 56 ], but they have not been explored for modRNA delivery.…”

“…Alternatively, small MW PEI with a similar chemical backbone to larger MW PEI has been functionalized with hydrophobic groups that led to superior delivery efficiency with acceptable biosafety [ 42 ]. These lipopolymers derived from low MW PEI were recently commercialized for a variety of uses with different nucleic acids [ 49 , 50 ].…”

siRNA Functionalized Lipid Nanoparticles (LNPs) in Management of Diseases

“…The result suggested that the co-delivery of lycopene with siRNA-loaded mPEGPCL-DDAB NPs can be considered a functional treatment for breast cancer [170]. In another study, different types of siRNAs (HSP90, CDC20, Mcl-1 and Survivin) were explored against MDA-MB-436 breast cancer cells [171]. The combination of Mcl-1 and surviving siRNA led to the suppression in the growth of cancer cells more effectively in comparison to single siRNAs [171,172].…”

“…In another study, different types of siRNAs (HSP90, CDC20, Mcl-1 and Survivin) were explored against MDA-MB-436 breast cancer cells [171]. The combination of Mcl-1 and surviving siRNA led to the suppression in the growth of cancer cells more effectively in comparison to single siRNAs [171,172].…”