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 in vivo 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.

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叶酸受体介导的 siRNA 递送：RNAi 疗法的最新发展和未来方向

RNA 干扰 (RNAi) 是一种由小干扰 RNA (siRNA) 介导的基因调控过程，作为一种潜在的治疗各种疾病的药物，已经取得了显着进展。然而，RNAi 与基本挑战有关，例如系统性传递不良和对核酸酶的敏感性。靶向配体结合的递送载体改善了药物在靶位点的积累，从而提高了转染效率并增强了基因沉默。最近，叶酸受体（FR）介导的siRNA靶向递送因其增强的细胞摄取和对肿瘤细胞的高转染效率而受到关注。叶酸（FA），由于其体积小、免疫原性低、体内高靶向 siRNA 的稳定性和对 FR 的高结合亲和力引起了人们的广泛关注。FR在大量肿瘤中过度表达，包括卵巢癌细胞、乳腺癌细胞、肾癌细胞和肺癌细胞。在这篇综述中，我们讨论了 FA 介导的 siRNA 递送治疗癌症和炎症性疾病的最新进展。本综述总结了迄今为止文献中报道的各种 FA 共轭纳米粒子系统，包括脂质体、二氧化硅、金属、石墨烯、树枝状大分子、壳聚糖、有机共聚物和 RNA 纳米粒子。本综述将有助于设计和开发使用 FR 介导的方法靶向肿瘤细胞的 siRNA 药物的潜在递送载体。