Wang Da, Sha Luping, Xu Chen, Huang Ying, Tang Chengcheng, Xu Tingting, Li Xianzhe, Di Donghua, Liu Jie, Yang Li
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
Colloids Surf B Biointerfaces. 2022 Jun;214:112448. doi: 10.1016/j.colsurfb.2022.112448. Epub 2022 Mar 14.
The application of saponins has been restricted by problems such as hemolysis, low bioavailability, and poor solubility. So it is imperative to find a strategy to deliver saponins safely and efficiently. Here, through bottom-up technique, we design and prepare two saponin-cholesterol (Cho) nano-complex: dioscin (Dio, steroid saponin)-Cho nanofibers (NFs) and escin Ia (EIa, triterpene saponin)-Cho nanoparticles (NPs). It is found that the hydrophobic force and hydrogen bonding drive the two pairs of molecules to bind in different directions (the 3β-OH of Cho face the sugar chain of EIa and the 22α-O of Dio, respectively) and finally show spherical NPs (EIa-Cho) and fibrous NFs (Dio-Cho). The equimolar saponin-Cho complex, Dio NFs and EIa NPs, reveal potent cytotoxicities against mouse breast cancer cells (4T1) in vitro. In vivo results confirm the antitumor (4T1 mice model) efficacy of PEGylation Dio NFs (10 mg/kg, i.v.) with a tumor inhibition rate of 61%, meanwhile, it does not cause extreme irritation and pain as free Dio does to mice. Moreover, compared with the free drug, the prepared nano-complex can significantly reduce hemolysis and organ toxicity. Our research reduces the toxicity of saponins while retaining their antitumor activity, providing a new strategy for the delivery of saponins.
皂苷的应用受到溶血、低生物利用度和低溶解度等问题的限制。因此，找到一种安全有效地递送皂苷的策略势在必行。在此，我们通过自下而上的技术设计并制备了两种皂苷 - 胆固醇（Cho）纳米复合物：薯蓣皂苷（Dio，甾体皂苷） - Cho纳米纤维（NFs）和七叶皂苷Ia（EIa，三萜皂苷） - Cho纳米颗粒（NPs）。研究发现，疏水力和氢键驱动这两对分子以不同方向结合（Cho的3β - OH分别朝向EIa的糖链和Dio的22α - O），最终呈现出球形纳米颗粒（EIa - Cho）和纤维状纳米纤维（Dio - Cho）。等摩尔的皂苷 - Cho复合物、Dio纳米纤维和EIa纳米颗粒在体外对小鼠乳腺癌细胞（4T1）显示出强大的细胞毒性。体内结果证实了聚乙二醇化Dio纳米纤维（10 mg/kg，静脉注射）对4T1小鼠模型的抗肿瘤功效，肿瘤抑制率为61%，同时，它不会像游离Dio那样对小鼠造成极度刺激和疼痛。此外，与游离药物相比，所制备的纳米复合物可显著降低溶血和器官毒性。我们的研究在保留皂苷抗肿瘤活性的同时降低了其毒性，为皂苷的递送提供了一种新策略。
