Bletilla striata Polysaccharide-Derived Nanomicelles for Co-Delivery of Andrographolide and Coixol: A Novel Strategy for Synergistic Targeted Treatment of Gastric Cancer

Abstract

Gastric cancer is a highly prevalent malignant tumor of the digestive system worldwide. Although andrographolide (AG) and coixol (CX) possess potential anti-gastric cancer effects, their clinical application is restricted by low bioavailability and poor targeting ability. Based on the meridian tropism theory of traditional Chinese medicine and the concept of “integrated drug and carrier”, this study constructed Bletilla striata polysaccharide-vitamin E succinate (BSP-VES) polymeric micelles co-loaded with AG and CX (AG&CX@BSP-VES) for synergistic targeted therapy of gastric cancer. In this study, AG&CX@BSP-VES was first systematically characterized in vitro to clarify its physicochemical properties, drug release behavior and hemolysis profile. Subsequently, using subcutaneous and orthotopic gastric cancer mouse models as research objects, in vitro cellular uptake and in vivo tumor targeting ability efficacy and biological safety of this drug delivery system were further evaluated. Results showed that the micelles were regularly spherical with a particle size of approximately 105 nm, exhibited favorable biological safety and asynchronous differential release characteristics, and could be specifically internalized by cells in vitro (which could be blocked by free BSP). In vivo, the accumulation of micelles in tumor masses was significantly higher than that in normal gastric tissues. Moreover, the cytotoxicity of the micelles against SGC-7901 tumor cells was remarkably higher than that of free AG or CX alone, which was attributed to enhanced cellular drug uptake and the synergistic effect between AG and CX. This study provides novel insights for the precise delivery of active ingredients from traditional Chinese medicine and individualized therapy of gastric cancer.