Abstract：
Leveraging liposomes for drug and nucleic acid delivery, though promising due to reduced toxicity and ease of preparation, faces challenges in stability and efficiency. To address this, we synthesized cationic amphiphiles from amino acids (arginine, lysine, and histidine). Histidine emerged as the superior candidate, leading to the development of three histidine-rich cationic amphiphiles for liposomes. Using the hydration method, we have prepared the liposomes and determined the optimal N/P ratios for lipoplex formation via gel electrophoresis. In vitro transfection assays compared the efficacy of our lipids to Fugene, while MTT assays gauged biocompatibility across cancer cell lines (MDA-MB 231 and MCF-7). The histidine-based lipid demonstrated marked potential in enhancing drug and nucleic acid delivery. This improvement stemmed from increased zeta potential, enhancing electrostatic interactions with nucleic acids and cellular uptake. Our findings underscore histidine\'s crucial role over lysine and arginine for effective delivery, revealing a significant correlation between histidine abundance and optimal performance. This study paves the way for histidine-enriched lipids as promising candidates for efficient drug and nucleic acid delivery, addressing key challenges in the field.
摘要：
利用脂质体进行药物和核酸递送，尽管由于毒性降低和易于制备，在稳定性和效率方面面临挑战。为了解决这个问题，我们从氨基酸(精氨酸，赖氨酸，和组氨酸）。组氨酸成为优越的候选者，导致开发三种富含组氨酸的阳离子两亲物用于脂质体。使用水合方法，我们已经制备了脂质体，并通过凝胶电泳确定了脂质复合物形成的最佳N/P比。体外转染试验比较了我们的脂质与Fugene的功效，而MTT测定测量了癌细胞系(MDA-MB231和MCF-7)的生物相容性。基于组氨酸的脂质显示出增强药物和核酸递送的显著潜力。这种改善源于增加的zeta电位，增强与核酸和细胞摄取的静电相互作用。我们的研究结果强调了组氨酸对于有效输送赖氨酸和精氨酸的关键作用，揭示了组氨酸丰度和最佳性能之间的显著相关性。这项研究为富含组氨酸的脂质作为有效药物和核酸递送的有希望的候选物铺平了道路。解决该领域的关键挑战。
