Targeted Delivery\nof BCL‑2 siRNA Using Modified\nFerritin Nanocarriers for Antitumor Therapy

In recent years, gene therapy has emerged as a promising\nstrategy\nfor combating tumors. However, the inherent instability and lack of\nspecificity of gene delivery systems pose significant challenges.\nTo address these limitations, we propose the development of a stable,\nefficient, and low-toxicity delivery nanoplatform with specific targeting\ncapabilities. Here, we utilize the ferritin cage, known for its inherent\nability to target transferrin receptor 1 (TfR1), as a nanocarrier\nfor gene delivery. Through genetic engineering and chemical coupling\nmethods, we modified the surface of ferritin with a cell-penetrating\npeptide (L17E) to enhance its cellular entry, resulting in the creation\nof Fn-L17E. This nanoplatform demonstrates improved physiological\nstability compared to wild-type ferritin (Fn). Furthermore, Fn-L17E\nloaded with BCL-2 siRNA exhibits enhanced silencing efficiency against\nBCL-2, a crucial antiapoptotic protein, in both A549 and HeLa cells,\nindicating its potential as an effective targeted gene delivery system\nfor antitumor therapy.