Lee Juhee, Jung Wookjin, Lee Dongkyu, Kang Mihyun, Chung Hyun Jung, Yeom Jihyeon
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
ACS Appl Mater Interfaces. 2025 Mar 26;17(12):18150-18159. doi: 10.1021/acsami.5c00920. Epub 2025 Mar 17.
mRNA therapeutics present a promising strategy for the treatment of human diseases, which requires a carrier to protect the mRNA and ensure its effective cellular delivery. However, research on how the surface physicochemical properties of the mRNA carriers affect the efficiency of delivery of mRNA into cells has been limited thus far. Here, we report that chirality control of lipid nanoparticles (LNPs) can enhance the delivery and transfection efficiency of cargo mRNA into cells. We prepared chiral LNPs by surface modification of LNPs with chiral cobalt oxide nanoparticles. The chiral LNPs with d- or l-chirality resulted in different cellular uptake and transfection efficiencies of luciferase or EGFP mRNA. Chiral LNPs with d-chirality showed significant enhancement in cellular delivery as well as transfection (5.3-fold) of mRNA compared to the control LNPs. This study suggests a novel strategy of using chirality for the delivery of nucleic acid drugs and provides a more in-depth understanding of the effect of chirality on cells.
信使核糖核酸（mRNA）疗法为人类疾病的治疗提供了一种很有前景的策略，这需要一种载体来保护mRNA并确保其有效地递送至细胞内。然而，迄今为止，关于mRNA载体的表面物理化学性质如何影响mRNA向细胞内递送效率的研究还很有限。在此，我们报告脂质纳米颗粒（LNP）的手性控制可提高货物mRNA向细胞内的递送和转染效率。我们通过用手性氧化钴纳米颗粒对LNP进行表面修饰来制备手性LNP。具有d-或l-手性的手性LNP导致荧光素酶或增强型绿色荧光蛋白（EGFP）mRNA的细胞摄取和转染效率不同。与对照LNP相比，具有d-手性的手性LNP在细胞递送以及mRNA转染方面（提高了5.3倍）表现出显著增强。这项研究提出了一种利用手性递送核酸药物的新策略，并提供了对手性对细胞影响的更深入理解。
