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

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...

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Detalles Bibliográficos
Autores: Sánchez Salcedo, Sandra, Vallet Regí, María Dulce Nombre, Allaf Shanin, Sophia, Zinck, Jeffrey I., Glackin, Carlotta A.
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/11948
Acceso en línea:https://hdl.handle.net/20.500.14352/11948
Access Level:acceso abierto
Palabra clave:546
615.46
Zwitterion
PEI core-shell MSNPs
Co-delivery
siRNA
Daunorubicin
Cancer therapy
Materiales
Química inorgánica (Química)
3312 Tecnología de Materiales
2303 Química Inorgánica
Descripción
Sumario: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 caused 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 cáncer.