Natural saponin and cholesterol assembled nanostructures as the promising delivery method for saponin

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.