  Mesoporous silica nanoparticles (MSNPs) have many potential applications in
biomedical fields. However, when MSNPs are exposed to plasma, protein
adsorption leads to opsonization and decreases blood circulation time. A new
multifunctional nanodevice based on polyethylenimine (PEI) coated core-shell
Fe3O4@SiO2 MSNPs with a zwitterionic 2-methacryloyloxyethyl phosphorylcholine
(MPC) surface was designed to minimize unspecific protein adhesion. Particle
size measurements demonstrated an excellent non-fouling capacity in solutions
containing Bovine Serum Albumin (BSA) and Fetal Bovine Serum (FBS) plasma
proteins. The system was used in this study to co-deliver two different cargos:
siRNA and daunorubicin. Anti-TWIST siRNA plays critical role in modulating
knockdown of TWIST and sensitizing cells to chemotherapeutics such as
daunorubicin for ovarian cancer therapy. The drug was released in response to
externally controlled oscillating magnetic fields (OMF). siRNA (siGFP) silenced
expression of green fluorescence protein (GFP) in Ovcar8 cancer cells,
demonstrating the incorporation of core shell MSNPs into cells and siGFP
delivery. The synergistic effect of the co-release of anti-TWIST-siRNA loaded
in the PEI and daunorubicin loaded in NPs pores c aused increased cytotoxicity
in Ovcar8 of up to 50% from both zwitteronic and non-zwitteronic NPs. The
system is the first example of silencing by anti-TWITS-siRNA /daunorubicin
co-delivered using zwitterionic core-shell nanoparticles with low-fouling
adsorption. This engineered multifunctional approach may provide therapeutic
potential for the treatment of currently incurable ovarian cancer.
