核糖核酸(RNA)药物在临床和临床前研究中对各种疾病显示出有希望的治疗效果,由于它们能够调节目的基因的表达或控制蛋白质合成。不同的策略,如化学改性,配体缀合,和纳米技术,为RNA医学的成功临床翻译做出了贡献,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)。其中,纳米技术可以保护RNA免受酶降解,增加细胞摄取和胞质运输,延长体循环,并改善组织/细胞靶向。这里,集中概述了用于RNA递送的刺激响应纳米技术,它们在促进RNA生物活性和细胞/器官选择性方面显示出独特的益处,提供。许多组织/细胞特异性微环境特征,如pH值,酶,缺氧,和氧化还原,用于设计内部刺激响应性RNA纳米颗粒(NP)。此外,外部刺激,如光,磁场,还有超声波,还用于控制RNA的释放和运输。这篇综述总结了用于RNA递送的各种刺激响应性NP系统,这可能会促进下一代RNA药物的开发。
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.