Functionally modified magnetic nanoparticles for effective siRNA delivery to prostate cancer cells in vitro

Abstract

Different types of siRNA delivery vehicles including nanoparticles have been synthesized and utilized for prostate cancer gene therapy. However, one of the most common limitations being faced is the toxicity of cationic polymers toward the cells. In the current study, magnetic nanoparticles were prepared and conjugated with cationic polymer, polyethylenimine. Then polyethylene glycol was conjugated with polyethylenimine to improve the biocompatibility of nanoparticles. The transmission electron microscopy size of nanoparticles was found to be 15.82 (±9.07) nm, while hydrodynamic size was about 79.20 (±0.68) nm. Zeta potential analysis of polyethylenimine and polyethylene glycol-coated nanoparticles was +31.4 (±0.62) and +5.65 (±0.76) mV, respectively. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance confirmed the presence of polyethylene glycol and polyethylenimine polymers in magnetic nanoparticles. Cell viability test in mouse fibroblast NIH 3T3 and prostate cancer PC3 cells showed an increased in biocompatibility of functionally modified polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles. siRNA targeting a disintegrin and metalloproteinase 10 (ADAM10) was successfully loaded into the polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles and delivered to PC3 cells. The results clearly demonstrated a significant decrease in cell viability, which increased within a certain siRNA concentration. The inhibitory concentration (IC50) value for ADAM10 siRNA was calculated to be 15.83 nM after 72 h. Confocal microscopy confirmed the delivery of siRNA-loaded nanoparticles intracellularly to the tumor cells cytosol. This magnetic system can be used as a powerful platform to inhibit cancer cells progression.

Advances in Targeting Cancer-Associated Genes by Designed siRNA in Prostate Cancer

“…Research revealed that knockdown of both RelA (also known as nuclear factor NFκB p65 subunit) and SRF by specific siRNAs through a non-virally modified cyclodextrin vector causes significant reductions in the invasion potential of the highly metastatic PC-3 cells, partly due to the reduction of MMP-9 [91]. Similar results in terms of a decrease in cell viability of PC-3 cells were achieved through a delivery of siRNAs targeting disintegrin and metalloproteinase 10 (ADAM10) by polyethylene glycolpolyethylenimine-Fe3O4 nanoparticles [92]. Furthermore, Choi et al [93] discovered that gene silence of Bcl-2, survivin, and androgen receptor with siRNAs, which are encapsulated in pluronic F-68 polymer, along with treatment with benzethonium chloride, triggers apoptosis of human PCa LNCaP-LN3 cells more efficiently in comparison with the silencing of individual gene, suggesting that multiple gene-targeting siRNA/drug delivery system could be a feasible and promising way to Owing to their unique and easy modification properties, dendrimers have emerged as a promising system for gene/drug delivery in cancer therapy [81,82].…”

Recent Advancements in the Design of Nanodelivery Systems of siRNA for Cancer Therapy

“…123 Panday et al designed iron oxide magnetic NCs (Fe 3 O 4 ) encapsulating PEI−PEG and loaded with disintegrin and metalloproteinase 10 (ADAM10) siRNA and released into the PC-3 cell line resulting in better cellular uptake and good biocompatibility to treat prostate cancer. 124 With a high transfection efficiency, the polycations PEI with a molecular weight of 25 kDa form polyplexes with the gene. However, the in vivo applications are constrained by the remarkable cytotoxicity and high positive charge.…”

An Overview of siRNA Delivery Strategies for Urological Cancers

“…The utilization of magnetic nanoparticles is commonly adopted for siRNA delivery systems. Recently, Fe 3 O 4 nanoparticles have been developed to deliver siRNA targeting metalloproteinase 10 (ADAM10) [97] in PC cells. ADAM10 is a secreted metalloproteinase involved in various physiological processes and in tumorigenesis.…”