With the rapid development of synthetic technology and biological technology, many nucleic acid‐based drugs have entered the clinical trials. However, their inherent disabilities in actively and efficiently penetrating cell membranes still severely restrict their further application. The main drawback of cationic lipids, which have been widely used as nonviral vectors of nucleic acids, is their high cytotoxicity. A series of nucleoside‐based or nucleotide‐based nucleolipids have been reported in recent years, due to their oligonucleotide delivery capacity and low toxicity in comparison with cationic lipids. Lipophilic prodrugs of nucleoside analogs have extremely similar structures with nucleolipid vectors and are thus helpful for improving the transmembrane ability. This review introduces the progress of nucleolipids and provides new strategies for improving the delivery efficiency of nucleic acid‐based drugs, as well as lipophilic prodrugs of nucleosides or nucleotides for antiviral or anticancer therapies.

中文翻译：

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克服寡核苷酸药物的递送障碍并提高核苷药物效率：核脂的使用。

随着合成技术和生物技术的飞速发展，许多核酸类药物已进入临床试验阶段。然而，它们在积极有效地穿透细胞膜方面的固有缺陷仍然严重限制了它们的进一步应用。已被广泛用作核酸的非病毒载体的阳离子脂质的主要缺点是它们的高细胞毒性。近年来，由于与阳离子脂质相比具有寡核苷酸递送能力和低毒性，已经报道了一系列基于核苷或基于核苷酸的核脂。核苷类似物的亲脂性前药与核脂载体具有极其相似的结构，因此有助于提高跨膜能力。