Mesoporous core-shell silica nanoparticles with anti-fouling properties for ovarian cancer therapy

TL;DR

This paper presents a novel multifunctional mesoporous silica nanoparticle system with anti-fouling properties, capable of co-delivering siRNA and chemotherapy drugs, demonstrating enhanced ovarian cancer cell targeting and treatment efficacy.

Contribution

Introduces a zwitterionic core-shell mesoporous silica nanoparticle with anti-fouling properties for co-delivering siRNA and daunorubicin, enabling targeted ovarian cancer therapy.

Findings

Excellent non-fouling capacity in plasma protein solutions

Successful co-delivery of siRNA and daunorubicin

Increased cytotoxicity in ovarian cancer cells

Abstract

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.