Department of Otolaryngology Head & Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China; Hearing Research Center, Southern Medical University, Guangzhou 510282, China.
Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.
Colloids Surf B Biointerfaces. 2022 Oct;218:112753. doi: 10.1016/j.colsurfb.2022.112753. Epub 2022 Aug 4.
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)-modified electrode arrays to deliver siRNA-TGFβ1 into the inner ear. The shape, diameter, pore diameter, and zeta potential of MSN-NH were investigated. siRNA loading capability and protective effect of MSN-NH were determined by agarose gel electrophoresis assay. The cytotoxicity, cellular uptake assay, and TGFβ1 knockdown efficiency of MSN-NH were studied by CCK-8 assay, flow cytometry, and real-time PCR, respectively. MSN-NH-siTGFβ1 nanoparticles were absorbed into the electrode arrays and worked in the cochleae. MSN-NH-siTGFβ1-modified CI electrode arrays may be an attractive therapeutic clinical intervention strategy to inhibit cochlear implantation fibrosis.
人工耳蜗植入物（CI）广泛应用于患者以恢复听力功能。TGFβ1 过度分泌引起的耳蜗内不受控制的纤维化严重影响了 CIs 的效果。siRNA 是一种下调 TGFβ1 的潜在治疗策略。然而，由于 siRNA 的穿透能力和稳定性差，以及耳蜗的不可及性和脆弱性，siRNA 在耳蜗中的治疗效果不佳。为了解决这些挑战，我们开发了氨基功能化介孔硅纳米粒子（MSN-NH）修饰的电极阵列，将 siRNA-TGFβ1 递送到内耳。研究了 MSN-NH 的形状、直径、孔径和 Zeta 电位。通过琼脂糖凝胶电泳试验确定了 MSN-NH 的 siRNA 负载能力和保护作用。通过 CCK-8 试验、流式细胞术和实时 PCR 分别研究了 MSN-NH 的细胞毒性、细胞摄取试验和 TGFβ1 下调效率。MSN-NH-siTGFβ1 纳米颗粒被吸收到电极阵列中，并在内耳中起作用。MSN-NH-siTGFβ1 修饰的 CI 电极阵列可能是一种有吸引力的治疗临床干预策略，可抑制耳蜗植入纤维化。
