Nucleic acid therapy is currently the most promising method for treating tumors and genetic diseases and for preventing infectious diseases. However, the biggest obstacle to this therapy is delivery of the nucleic acids to the target site, which requires overcoming problems such as capture by the immune system, the need to penetrate biofilms, and degradation of nucleic acid performance. Designing suitable delivery vectors is key to solving these problems. Lipids—which consist of a hydrophilic headgroup, a linker, and a hydrophobic tail—are crucial components for the construction of vectors. The headgroup is particularly important because it affects the drug encapsulation rate, the vector cytotoxicity, and the transfection efficiency. Herein, we focus on various headgroup structures (tertiary amines, quaternary ammonium salts, peptides, piperazines, dendrimers, and several others), and we summarize and classify important lipid-based carriers that have been developed in recent years. We also discuss applications of cationic lipids with various headgroups for delivery of nucleic acid drugs, and we analyze how headgroup structure affects transport efficiency and carrier toxicity. Finally, we briefly describe the challenges of developing novel lipid carriers, as well as their prospects.

中文翻译：

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核酸治疗用脂质亲水头基的开发及应用


核酸治疗是目前治疗肿瘤、遗传性疾病和预防传染病最有前景的方法。然而，这种疗法的最大障碍是将核酸递送至靶位点，这需要克服诸如被免疫系统捕获、需要穿透生物膜以及核酸性能退化等问题。设计合适的递送载体是解决这些问题的关键。脂质由亲水性头基、连接基和疏水性尾部组成，是载体构建的关键组成部分。头基尤其重要，因为它影响药物包封率、载体细胞毒性和转染效率。在此，我们重点关注各种头基结构（叔胺、季铵盐、肽、哌嗪、树枝状大分子等），并对近年来开发的重要脂质载体进行总结和分类。我们还讨论了具有各种头基的阳离子脂质在核酸药物递送中的应用，并分析了头基结构如何影响运输效率和载体毒性。最后，我们简要描述了开发新型脂质载体的挑战及其前景。