1.Precise delivery of obeticholic acid
Guofeng JI ; Lushun MA ; Haochen YAO ; Sheng MA ; Xinghui SI ; Yalin WANG ; Xin BAO ; Lili MA ; Fangfang CHEN ; Chong MA ; Leaf HUANG ; Xuedong FANG ; Wantong SONG
Acta Pharmaceutica Sinica B 2020;10(11):2171-2182
Primary bile acids were reported to augment secretion of chemokine (C‒X‒C motif) ligand 16 (CXCL16) from liver sinusoidal endothelial cells (LSECs) and trigger natural killer T (NKT) cell-based immunotherapy for liver cancer. However, abundant expression of receptors for primary bile acids across the gastrointestinal tract overwhelms the possibility of using agonists against these receptors for liver cancer control. Taking advantage of the intrinsic property of LSECs in capturing circulating nanoparticles in the circulation, we proposed a strategy using nanoemulsion-loaded obeticholic acid (OCA), a clinically approved selective farnesoid X receptor (FXR) agonist, for precisely manipulating LSECs for triggering NKT cell-mediated liver cancer immunotherapy. The OCA-nanoemulsion (OCA-NE) was prepared