Department of Cardiology, Clinical Trial Center, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, 430071, Wuhan, China.
Center for Nanomedicine and Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Adv Sci (Weinh). 2023 Dec;10(36):e2303597. doi: 10.1002/advs.202303597. Epub 2023 Nov 1.
Ribonucleic acid (RNA) drugs have shown promising therapeutic effects for various diseases in clinical and preclinical studies, owing to their capability to regulate the expression of genes of interest or control protein synthesis. Different strategies, such as chemical modification, ligand conjugation, and nanotechnology, have contributed to the successful clinical translation of RNA medicine, including small interfering RNA (siRNA) for gene silencing and messenger RNA (mRNA) for vaccine development. Among these, nanotechnology can protect RNAs from enzymatic degradation, increase cellular uptake and cytosolic transportation, prolong systemic circulation, and improve tissue/cell targeting. Here, a focused overview of stimuli-responsive nanotechnologies for RNA delivery, which have shown unique benefits in promoting RNA bioactivity and cell/organ selectivity, is provided. Many tissue/cell-specific microenvironmental features, such as pH, enzyme, hypoxia, and redox, are utilized in designing internal stimuli-responsive RNA nanoparticles (NPs). In addition, external stimuli, such as light, magnetic field, and ultrasound, have also been used for controlling RNA release and transportation. This review summarizes a wide range of stimuli-responsive NP systems for RNA delivery, which may facilitate the development of next-generation RNA medicines.
核糖核酸（RNA）药物在临床和临床前研究中显示出对各种疾病有很有前景的治疗效果，这是因为它们能够调节感兴趣的基因的表达或控制蛋白质的合成。不同的策略，如化学修饰、配体偶联和纳米技术，都有助于 RNA 药物的成功临床转化，包括用于基因沉默的小干扰 RNA（siRNA）和用于疫苗开发的信使 RNA（mRNA）。在这些策略中，纳米技术可以保护 RNA 免受酶降解，增加细胞摄取和细胞质运输，延长系统循环，并提高组织/细胞靶向性。在这里，我们重点介绍了用于 RNA 递送的响应性纳米技术，这些技术在促进 RNA 生物活性和细胞/组织选择性方面具有独特的优势。许多组织/细胞特异性的微环境特征，如 pH 值、酶、缺氧和氧化还原等，都被用于设计内部响应性 RNA 纳米颗粒（NPs）。此外，外部刺激，如光、磁场和超声，也被用于控制 RNA 的释放和运输。本综述总结了广泛的用于 RNA 递送的响应性 NP 系统，这可能有助于开发下一代 RNA 药物。
