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.
AttardGParkerCEelesRA, et al.
Prostate cancer. Lancet2016;
387: 70–82.
2.
NageshPKBJohnsonNRBoyaVKN, et al.
PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer. Coll Surf B Biointerf2016;
144: 8–20.
3.
SannaVSechiM.Nanoparticle therapeutics for prostate cancer treatment. Maturitas2012;
73: 27–32.
4.
KangLGaoZHuangW, et al.
Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment. Acta Pharm Sin B2015;
5: 169–175.
5.
NedyalkovaMDonkovaBRomanovaJ, et al.
Iron oxide nanoparticles—In vivo/in vitro biomedical applications and in silico studies. Adv Coll Interf Sci2017;
249: 192–212.
6.
XieYQiaoHSuZ, et al.
PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy. Biomaterials2014;
35: 7978–7991.
7.
CavallaroGSardoCCraparoEF, et al.
Polymeric nanoparticles for siRNA delivery: production and applications. Int J Pharm2017;
525: 313–333.
8.
EweAHöbelSHeineC, et al. Optimized polyethylenimine (PEI)-based nanoparticles for siRNA delivery, analyzed in vitro and in an ex vivo tumor tissue slice culture model. Drug Deliv Transl Res 2017; 7: 206–216.
9.
LeeSJYookSYheeJY, et al.
Co-delivery of VEGF and Bcl-2 dual-targeted siRNA polymer using a single nanoparticle for synergistic anti-cancer effects in vivo. J Control Rel2015;
220: 631–641.
10.
ArifTVasilkovskyLRefaelyY, et al.
Silencing VDAC1 expression by siRNA inhibits cancer cell proliferation and tumor growth in vivo. Mol Ther Nucleic Acids2014;
3: e159.
11.
LiJZhengLCaiH, et al.
Polyethyleneimine-mediated synthesis of folic acid-targeted iron oxide nanoparticles for invivo tumor MR imaging. Biomaterials2013;
34: 8382–8392.
12.
RyuNKimMAParkD, et al.
Effective PEI-mediated delivery of CRISPR-Cas9 complex for targeted gene therapy. Nanomed Nanotechnol Biol Med2018;
14: 2095–2102.
13.
LiuSZhangWLiuK, et al.
Synergistic effects of co-expression plasmid-based ADAM10-specific siRNA and GRIM-19 on hepatocellular carcinoma in vitro and in vivo. Oncol Rep2014;
32: 2501–2510.
14.
MazzoccaAGiannelliGAntonaciS.Involvement of ADAMs in tumorigenesis and progression of hepatocellular carcinoma: Is it merely fortuitous or a real pathogenic link?Biochim Biophys Acta Rev Cancer2010;
1806: 74–81.
15.
QuMINQiuBOXiongW, et al. Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma. Oncol Lett 2015; 9: 2157–2162.
16.
ArimaTEnokidaHKuboH, et al.
Nuclear translocation of ADAM-10 contributes to the pathogenesis and progression of human prostate cancer. Cancer Sci2007;
98: 1720–1726.
ZhuLBZhaoSTXuTZ, et al.
Tumor necrosis factor-α-induced a disintegrin and metalloprotease 10 increases apoptosis resistance in prostate cancer cells. Oncol Lett2014;
7: 897–901.
19.
WuCGongFPangP, et al.
An RGD-modified MRI-visible polymeric vector for targeted siRNA delivery to hepatocellular carcinoma in nude mice. PLoS One2013;
8: 1–13.
20.
KyungCCJiHJHyunJC, et al.
Folate receptor-mediated intracellular delivery of recombinant caspase-3 for inducing apoptosis. J Control Rel2005;
108: 121–131.
21.
HoKMLiP.Design and synthesis of novel magnetic core-shell polymeric particles. Langmuir2008;
24: 1801–1807.
22.
LakshmananRSanchez-DominguezMMatutes-AquinoJA, et al. Removal of total organic carbon from sewage wastewater using poly(ethylenimine)-functionalized magnetic nanoparticles. Langmuir 2014; 304: 1036–1044.
23.
ParkJWBaeKHKimC, et al.
Clustered magnetite nanocrystals cross-linked with PEI for efficient siRNA delivery. Biomacromolecules2011;
12: 457–465.
24.
KoSYLinSCWongYK, et al.
Increase of disintergin metalloprotease 10 (ADAM10) expression in oral squamous cell carcinoma. Cancer Lett2007;
245: 33–43.
25.
HuangYMaoKZhangB, et al.
Superparamagnetic iron oxide nanoparticles conjugated with folic acid for dual target-specific drug delivery and MRI in cancer theranostics. Mater Sci Eng C2017;
70: 763–771.
26.
DoMAYoonGJYeumJH, et al.
Polyethyleneimine-mediated synthesis of superparamagnetic iron oxide nanoparticles with enhanced sensitivity in T2magnetic resonance imaging. Coll Surf B Biointerf2014;
122: 752–759.
27.
WangJZhangBWangL, et al.
One-pot synthesis of water-soluble superparamagnetic iron oxide nanoparticles and their MRI contrast effects in the mouse brains. Mater Sci Eng C2015;
48: 416–423.
28.
ElbialyNSFathyMMKhalilWM.Preparation and characterization of magnetic gold nanoparticles to be used as doxorubicin nanocarriers. Phys Medica2014;
30: 843–848.
29.
WangXZhuLHouX, et al. Polyethylenimine mediated magnetic nanoparticles for combined intracellular imaging, siRNA delivery and anti-tumor therapy. RSC Adv 2015; 5: 101569–101581.
30.
SteitzBHofmannHKamauSW, et al.
Characterization of PEI-coated superparamagnetic iron oxide nanoparticles for transfection: size distribution, colloidal properties and DNA interaction. J Magn Magn Mater2007;
311: 300–305.
31.
RejmanJOberleVZuhornIS, et al.
Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J2004;
377: 159–169.
32.
MogoşanuGDGrumezescuAMBejenaruC, et al.
Polymeric protective agents for nanoparticles in drug delivery and targeting. Int J Pharm2016;
510: 419–429.
33.
PengJZouFLiuL, et al.
Preparation and characterization of PEG-PEI/Fe3O4 nano-magnetic fluid by co-precipitation method. Trans Nonferrous Met Soc China2008;
18: 393–398.
34.
ChenYLianGLiaoC. Characterization of polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) as an MRI-visible vector for siRNA delivery in gastric cancer in vitro and in vivo. J Gastroenterol 2013; 48: 809–821.
35.
FitzsimmonsREBUludağH.Specific effects of PEGylation on gene delivery efficacy of polyethylenimine: interplay between PEG substitution and N/P ratio. Acta Biomater2012;
8: 3941–3955.
36.
PopescuLMPiticescuRMPetriceanuM, et al.
Hydrothermal synthesis of nanostructured hybrids based on iron oxide and branched PEI polymers. In fluence of high pressure on structure and morphology. Mater Chem Phys2015;
161: 84–95.
37.
SoodAAroraVShahJ, et al.
Multifunctional gold coated iron oxide core-shell nanoparticles stabilized using thiolated sodium alginate for biomedical applications. Mater Sci Eng C2017;
80: 274–281.
38.
JoubranSZiglerMPessahN, et al. Optimization of liganded polyethylenimine polyethylene glycol 2 vector for nucleic acid delivery. Bioconjugate Chem 2014; 259: 1644–1654.
39.
CaiHAnXCuiJ, et al.
Facile hydrothermal synthesis and surface functionalization of polyethyleneimine-coated iron oxide nanoparticles for biomedical applications. ACS Appl Mater Interf2013;
5: 1722–1731.
40.
QiLWuLZhengS, et al.
Cell-penetrating magnetic nanoparticles for highly efficient delivery and intracellular imaging of siRNA. Biomacromolecules2012;
13: 2723–2730.
