Targeted Delivery of BCL-2 siRNA Using Modified Ferritin Nanocarriers for Antitumor Therapy

In recent years, gene therapy has emerged as a promising strategy for combating tumors. However, the inherent instability and lack of specificity of gene delivery systems pose significant challenges. To address these limitations, we propose the development of a stable, efficient, and low-toxicity delivery nanoplatform with specific targeting capabilities. Here, we utilize the ferritin cage, known for its inherent ability to target transferrin receptor 1 (TfR1), as a nanocarrier for gene delivery. Through genetic engineering and chemical coupling methods, we modified the surface of ferritin with a cell-penetrating peptide (L17E) to enhance its cellular entry, resulting in the creation of Fn-L17E. This nanoplatform demonstrates improved physiological stability compared to wild-type ferritin (Fn). Furthermore, Fn-L17E loaded with BCL-2 siRNA exhibits enhanced silencing efficiency against BCL-2, a crucial antiapoptotic protein, in both A549 and HeLa cells, indicating its potential as an effective targeted gene delivery system for antitumor therapy.