在这项研究中，我们合成了一种新型化合物，胍丁胺-胆固醇缀合物（AG-Chol），以增强载药脂质体的抗肿瘤活性。我们采用主动负载法制备盐酸阿霉素（DOX）脂质体，用AG-Chol代替胆固醇。我们评估了所得 AG 脂质体的物理和化学性质，并评估了其体外和体内功效。结果表明，AG-脂质体稳定性好，包封率高。与对照脂质体相比，AG-脂质体在pH 6.8的释放介质中表现出较慢的药物释放速率。体外细胞实验表明，AG-脂质体比对照脂质体具有更高的肿瘤细胞摄取率、更强的迁移抑制率、更高的凋亡率、更好的抗克隆形成能力和更高的溶酶体逃逸能力。体内分布结果表明，用AG-Chol代替胆固醇制备的脂质体可以显着增强其肿瘤靶向能力并减少其向非靶向部位的分布。体内肿瘤抑制实验表明，AG-脂质体比对照脂质体具有更高的肿瘤抑制率，且组织学染色证明不对正常组织产生明显的毒性。因此，在制备脂质体时用 AG-Chol 替代胆固醇可以增强溶酶体逃逸，改善肿瘤靶向性并提高抗肿瘤药物的疗效。© 2023。控释协会。

In this study, we synthesized a novel compound, agmatine-cholesterol conjugate (AG-Chol), to enhance the anti-tumor activity of drug-loaded liposomes. We replaced cholesterol with AG-Chol in preparing doxorubicin hydrochloride (DOX) liposomes by using an active loading method for DOX. We assessed the physical and chemical properties of the resulting AG-Liposomes and evaluated their efficacy in vitro and in vivo. The results showed that AG-Liposomes were stable with high encapsulation efficiency. Compared with the control liposomes, AG-Liposomes exhibited a slower drug release rate in the release medium at pH 6.8. The in vitro cell experiments demonstrated that AG-Liposomes had higher tumor cell uptake rate, stronger migration inhibition rate, higher apoptosis rate, better anti-clonogenic ability, and higher lysosome escape ability than the control liposomes. In vivo distribution results demonstrate that liposomes prepared with AG-Chol instead of cholesterol can significantly enhance their tumor targeting abilities and reduce their distribution to non-targeted sites. In vivo tumor suppression experiments showed that AG-Liposomes had a higher tumor suppression rate than the control liposomes without causing apparent toxicity to normal tissues, as evidenced by histological staining. Therefore, substituting cholesterol with AG-Chol in the preparation of liposomes can result in enhanced lysosome escape, improved tumor targeting, and increased efficacy of anti-tumor drugs.© 2023. Controlled Release Society.