RNA interference (RNAi) technology has become a powerful tool in application of unraveling the mechanism of disease and may hold the potential to be developed for clinical uses. Small interfering RNA (siRNA) can bind to target mRNA with high specificity and efficacy and thus inhibit the expression of related protein for the purpose of treatment of diseases. The major challenge for RNAi application is how to improve its stability and bioactivity and therefore deliver therapeutic agents to the target sites with high efficiency and accuracy. PEGylated lipid-based delivery system has been widely used for development of various medicines due to its long circulating half-life time, low toxicity, biocompatibility, and easiness to be scaled up. The PEGylated lipid-based delivery system may also provide platform for targeting delivery of nucleic acids, and some of the research works have moved to the phases for clinical trials. In this review, we introduced the mechanism, major challenges, and strategies to overcome technical barriers of PEGylated lipid-based delivery systems for advanced target delivery of siRNA in vivo. We also summarized recent advance of PEGylated lipid-based siRNA delivery systems and included some successful research works in this field.

RNA干扰（RNAi）技术已成为揭示疾病机理的强大工具，并具有开发用于临床的潜力。小干扰RNA（siRNA）可以高特异性和高效率结合靶mRNA，从而抑制相关蛋白的表达以治疗疾病。RNAi应用的主要挑战是如何提高其稳定性和生物活性，并因此将治疗剂高效高效地递送至靶位。基于聚乙二醇化脂质的递送系统，由于其循环半衰期长，毒性低，生物相容性好，易于扩展等优点，已被广泛用于各种药物的开发。基于PEG化脂质的递送系统还可提供靶向核酸递送的平台，一些研究工作已经进入临床试验阶段。在这篇综述中，我们介绍了克服基于PEG脂质的基于siRNA的目标递送系统的技术障碍的机制，主要挑战和策略体内。我们还总结了基于聚乙二醇化脂质的siRNA递送系统的最新进展，并包括该领域的一些成功研究工作。