Li Ningyu, Dong Fan, Sun Lisha, Qian Yuping, Zhang Ludan, Wang Guiyan, Yuan Lintian, Liu Hong, Jiang Yong, Wang Yuguang
Department of General Dentistry, Hospital of Stomatology, Jilin University, Changchun 130012, China.
Center of Digital Dentistry, Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & NHC Research Center of Engineering and Technology for Computerized Dentistry, Beijing 100081, China.
Fundam Res. 2024 Mar 28;5(4):1698-1709. doi: 10.1016/j.fmre.2024.03.014. eCollection 2025 Jul.
Activated anti-oxidation reactions in cells partially diminish the anticancer effect of photodynamic therapy (PDT), significantly hindering efforts to increase the efficacy of PDT. The expression of transcription factor E2 related factor 2 (Nrf2), an important redox-regulated transcription factor, can be downregulated by Nrf2 siRNA, leading to greatly enhanced PDT effects. However, the efficient co-delivery of photosensitizers and siRNAs remains a key problem because these agents are complex to synthesize, exhibit poor biocompatibility and load drugs with a low efficiency. Herein, we designed a carrier-free and extremely simple strategy to co-deliver a photosensitizer and Nrf2 siRNA to cancer cells. In this nanoplatform, an indocyanine green photosensitizer, siRNA and FeⅡ were self-assembled to form a spherical hybrid structure with a uniform size, high loading ratio and adjustable component ratio. The platform can effectively transfer photosensitizers and siRNAs into cells and effectively inhibit tumour growth . Overall, the self-assembly approach shows great potential for clinical application and provides a simple method to achieve photodynamic therapy and enhanced photothermal therapy.
细胞内激活的抗氧化反应会部分削弱光动力疗法（PDT）的抗癌效果，严重阻碍提高PDT疗效的努力。转录因子E2相关因子2（Nrf2）是一种重要的氧化还原调节转录因子，其表达可被Nrf2 siRNA下调，从而导致PDT效果大大增强。然而，由于这些药物合成复杂、生物相容性差且载药效率低，因此光敏剂和siRNAs的高效共递送仍然是一个关键问题。在此，我们设计了一种无载体且极其简单的策略，将光敏剂和Nrf2 siRNA共递送至癌细胞。在这个纳米平台中，吲哚菁绿光敏剂、siRNA和FeⅡ自组装形成具有均匀尺寸、高负载率和可调节组成比例的球形杂化结构。该平台可有效地将光敏剂和siRNAs转运到细胞中，并有效抑制肿瘤生长。总体而言，这种自组装方法显示出巨大的临床应用潜力，并提供了一种实现光动力疗法和增强光热疗法的简单方法。
