Development of drug resistance to anticancer drugs is an important challenge
for cancer treatment. Recent studies focus on co-delivery of anticancer drugs
and siRNA to overcome this challenge. Mesoporous silica nanoparticles (MSNs) are
one of the promising nanoparticles that enable the delivery of drugs and siRNA simultaneously.
MSNs coated with copolymer capable of co-delivery of drug and
siRNA were prepared and characterized. In the present study, MSNs functionalized
with polyethylenimine-polyethylene glycol (PEI-PEG) copolymer were prepared.
MSNs were characterized using dynamic light scattering (DLS), Transmission Electron
Microscopy (TEM) and elemental analysis. Nanoparticles were loaded with epirubicin
hydrochloride (EPI) and anti B-cell lymphoma 2 (BCL-2) siRNA. The in
vitro cytotoxicity and in vivo efficacy of different formulations were evaluated. Mean size of MSNs
ranged from 98 to 247 nm. EPI release from MSNs was pH-dependent. MSNs loaded with EPI and
siRNA showed better in vitro cytotoxicity with 1 μg/mL EPI and 50-400 ng/mL siRNA, besides MSNs
loaded with 9 mg/kg EPI and 1.2 mg/kg siRNA resulted in improved in vivo effects compared to EPI or
MSNs containing EPI or siRNA alone. The results of in vitro and in vivo studies indicated the synergistic
effect of EPI and anti BCL-2 siRNA. This formulation could be a promising nanoparticle for codelivery
of drug and siRNA in cancer cells.
Keywords: BCL-2, Cancer treatment, Co-delivery, Epirubicin, Mesoporous silica nanoparticles, siRNA.
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