Gangopadhyay Sumit, Nikam Rahul R, Gore Kiran R
Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur, India.
Department of Chemistry, University of Mumbai, Mumbai, India.
Nucleic Acid Ther. 2021 Aug;31(4):245-270. doi: 10.1089/nat.2020.0882. Epub 2021 Feb 15.
RNA interference (RNAi), a gene regulatory process mediated by small interfering RNAs (siRNAs), has made remarkable progress as a potential therapeutic agent against various diseases. However, RNAi is associated with fundamental challenges such as poor systemic delivery and susceptibility to the nucleases. Targeting ligand-bound delivery vehicles has improved the accumulation of drug at the target site, which has resulted in high transfection efficiency and enhanced gene silencing. Recently, folate receptor (FR)-mediated targeted delivery of siRNAs has garnered attention due to their enhanced cellular uptake and high transfection efficiency toward tumor cells. Folic acid (FA), due to its small size, low immunogenicity, high stability, and high binding affinity toward FRs, has attracted much attention for targeted siRNA delivery. FRs are overexpressed in a large number of tumors, including ovarian, breast, kidney, and lung cancer cells. In this review, we discuss recent advances in FA-mediated siRNA delivery to treat cancers and inflammatory diseases. This review summarizes various FA-conjugated nanoparticle systems reported so far in the literature, including liposome, silica, metal, graphene, dendrimers, chitosan, organic copolymers, and RNA nanoparticles. This review will help in the design and development of potential delivery vehicles for siRNA drug targeting to tumor cells using an FR-mediated approach.
RNA干扰（RNAi）是一种由小干扰RNA（siRNA）介导的基因调控过程，作为一种针对各种疾病的潜在治疗剂已取得显著进展。然而，RNAi存在一些根本性挑战，如全身递送效果不佳和易受核酸酶影响。靶向配体结合的递送载体提高了药物在靶位点的积累，从而导致高转染效率和增强的基因沉默。最近，叶酸受体（FR）介导的siRNA靶向递送因其对肿瘤细胞的细胞摄取增强和高转染效率而受到关注。叶酸（FA）因其体积小、免疫原性低、稳定性高以及对FRs的高结合亲和力，在靶向siRNA递送方面备受关注。FRs在包括卵巢癌、乳腺癌、肾癌和肺癌细胞在内的大量肿瘤中过表达。在本综述中，我们讨论了FA介导的siRNA递送在治疗癌症和炎症性疾病方面的最新进展。本综述总结了迄今为止文献中报道的各种FA缀合纳米颗粒系统，包括脂质体、二氧化硅、金属、石墨烯、树枝状聚合物、壳聚糖、有机共聚物和RNA纳米颗粒。本综述将有助于设计和开发潜在的递送载体，用于通过FR介导的方法将siRNA药物靶向肿瘤细胞。
