Mesoporous silica nanoparticle-modified electrode arrays of cochlear implants for delivery of siRNA-TGFβ1 into the inner ear

Cochlear implants (CI) are widely used in patients to restore hearing function. Uncontrolled fibrosis in the cochleae induced by excess secretion of TGFβ1 seriously affects the effectiveness of CIs. siRNA is a potential therapeutic strategy to downregulate TGFβ1 specifically. However, treatment with siRNA in cochleae is difficult due to the poor penetration capability and instability of siRNA and the inaccessibility and vulnerability of cochleae. To address these challenges, we developed amino-functionalized mesoporous silica nanoparticle (MSN-NH 2 )-modified electrode arrays to deliver siRNA-TGFβ1 into the inner ear. The shape, diameter, pore diameter, and zeta potential of MSN-NH 2 were investigated. siRNA loading capability and protective effect of MSN-NH 2 were determined by agarose gel electrophoresis assay. The cytotoxicity, cellular uptake assay, and TGFβ1 knockdown efficiency of MSN-NH 2 were studied by CCK-8 assay, flow cytometry , and real-time PCR, respectively. MSN-NH 2 -siTGFβ1 nanoparticles were absorbed into the electrode arrays and worked in the cochleae. MSN-NH 2 -siTGFβ1-modified CI electrode arrays may be an attractive therapeutic clinical intervention strategy to inhibit cochlear implantation fibrosis.