Chiral and Dual Drugs Combination Reduces Tumor-Associated Neutrophils-Induced T-Cell Immunoparalysis to Treat Epithelial Ovarian Cancer.

In antitumor activities, baicalin and astragaloside IV inhibit tumor growth, induce cell death, and restrain metastasis in various cancers. Generally, a mixture of massive herbs like scutellaria or astragalus matches with other drugs to reach a curative effect in traditional Chinese prescription. Therefore, researchers aspire to an effective type of drug combination that shows promoted absorption and higher bioavailability in preclinical studies. Here, we report an optical method to detect chiral baicalin and astragaloside IV and also monitor the absorption of different chirals in ovarian cells. Eventually, R-Baicalin-Astragaloside IV dual drugs combination shows promoted absorption of each other compared with single chiral drugs or another. Based on the optical method results, we designed a series of in vitro and in vivo experiments to explain and analyze the mechanism of the curative effect. Therein, the result reveals that the tumor-associated neutrophils were reduced via the down-regulated TLR4/MYD88/NF-κB pathway to increased PD-1/PD-L1 immune response in epithelial ovarian cancer under the influence of R-Baicalin-Astragaloside IV. Thus, this work offers a comprehensive report on structure-activity relationships of chiral and dual drug strategies to improve its bioavailability in therapy of ovarian cancer.