Abstract
Tamibarotene (Am80) is a promising anti-tumor drug that induces the expression of Meflin (a glycosylphosphatidyl inositol-anchored protein) in cancer-associated fibroblasts, thereby improving the tumor microenvironment. However, Am80, which is approved only for oral administration owing to its poor water solubility, has the challenge of poor tumor penetration. In this study, we developed poly(lactic-co-glycolic acid) nanoparticles loaded with Am80 (Am80-PLGA nanoparticles) as a potential intravenous drug for targeted Am80 delivery to the tumor site. The Am80-PLGA nanoparticles were fabricated using the single-emulsion method in the presence of cationic polyethyleneimine (PEI). The loading efficiency of Am80 in the nanoparticles was controlled by tuning the PEI concentration in the preparation mixture. Nanoparticles with the highest Am80-loading efficiency were dispersible and showed a hydrodynamic diameter of approximately 190 nm in phosphate-buffered saline for up to 2 weeks. The Am80 release from the nanoparticles started in a day and lasted for weeks. The nanoparticles upregulated Meflin expression in human fibroblasts (fHDF/TERT166 cells). These results suggest the potential of Am80-PLGA nanoparticles as a new intravenous anti-tumor drug that can improve the tumor microenvironment, thereby enhancing the efficacy of chemotherapy and immunotherapy.