Ewert Kai K, Scodeller Pablo, Simón-Gracia Lorena, Steffes Victoria M, Wonder Emily A, Teesalu Tambet, Safinya Cyrus R
Materials, Physics, and Molecular, Cellular, and Developmental Biology Departments, and Biomolecular Science and Engineering Program, University of California at Santa Barbara, Santa Barbara, CA 93106, USA.
Laboratory of Precision- and Nanomedicine, Institute of Biomedicine and Translational Medicine, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 14b, 50411 Tartu, Estonia.
Pharmaceutics. 2021 Aug 30;13(9):1365. doi: 10.3390/pharmaceutics13091365.
Cationic liposomes (CLs) are effective carriers of a variety of therapeutics. Their applications as vectors of nucleic acids (NAs), from long DNA and mRNA to short interfering RNA (siRNA), have been pursued for decades to realize the promise of gene therapy, with approvals of the siRNA therapeutic patisiran and two mRNA vaccines against COVID-19 as recent milestones. The long-term goal of developing optimized CL-based NA carriers for a broad range of medical applications requires a comprehensive understanding of the structure of these vectors and their interactions with cell membranes and components that lead to the release and activity of the NAs within the cell. Structure-activity relationships of lipids for CL-based NA and drug delivery must take into account that these lipids act not individually but as components of an assembly of many molecules. This review summarizes our current understanding of how the choice of the constituting lipids governs the structure of their CL-NA self-assemblies, which constitute distinct liquid crystalline phases, and the relation of these structures to their efficacy for delivery. In addition, we review progress toward CL-NA nanoparticles for targeted NA delivery in vivo and close with an outlook on CL-based carriers of hydrophobic drugs, which may eventually lead to combination therapies with NAs and drugs for cancer and other diseases.
阳离子脂质体（CLs）是多种治疗药物的有效载体。几十年来，人们一直致力于将其用作核酸（NAs）的载体，从长链DNA和mRNA到短干扰RNA（siRNA），以实现基因治疗的前景，近期的里程碑是siRNA治疗药物帕替拉韦钠的获批以及两种抗COVID-19的mRNA疫苗的获批。开发用于广泛医学应用的优化的基于CL的NA载体的长期目标需要全面了解这些载体的结构及其与细胞膜和导致NA在细胞内释放和活性的成分的相互作用。基于CL的NA和药物递送的脂质构效关系必须考虑到这些脂质并非单独起作用，而是作为许多分子组装体的组成部分。本综述总结了我们目前对构成脂质的选择如何控制其CL-NA自组装结构的理解，这些自组装构成了不同的液晶相，以及这些结构与其递送功效的关系。此外，我们回顾了用于体内靶向NA递送的CL-NA纳米颗粒的进展，并展望了基于CL的疏水药物载体，这最终可能导致NA和药物联合治疗癌症和其他疾病。
