Small interfering RNAs (siRNAs) can selectively target and downregulate disease-causing genes, holding great promise in treating human diseases, especially malignant cancers. However, how to efficiently deliver siRNAs into target cell cytosol is a problem that has hindered their clinical application. Here, we review the recent strategies for siRNA delivery on the basis of smart nanocarriers by using stimuli-responsive materials. We highlight the rationales of how to design smart nanocarriers responsive to physiological and external stimuli to improve the delivery efficiency, targeting precision and gene silencing efficacy. Finally, we provide an outlook on the fundamental limitation for clinical translation of siRNA-based nanomedicine that should be overcome by the combination of chemistry, biology, material and medical science.

小型干扰RNA（siRNA）可以选择性靶向和下调致病基因，在治疗人类疾病尤其是恶性癌症方面具有广阔的前景。然而，如何有效地将siRNA递送至靶细胞胞质溶胶是阻碍其临床应用的问题。在这里，我们通过使用刺激响应材料，回顾基于智能纳米载体的siRNA递送的最新策略。我们重点介绍了如何设计能够响应生理和外部刺激的智能纳米载体，以提高递送效率，靶向精度和基因沉默功效的基本原理。最后，我们对基于siRNA的纳米药物临床翻译的基本局限性提出了展望，应该通过化学，生物学，材料和医学科学的结合来克服这一局限性。