A "cluster bomb" oral drug delivery system to sequentially overcome the multiple absorption barriers

Oral drugs have been widely used in clinical therapy, but their developments were severely limited by the side effects of drug exposure as well as the multiple biological barriers. In this study, we constructed a "cluster bomb" oral drug delivery system (DOX@PFeL@L100) with core-shell structure to overcome the complex absorption barriers. The inner core termed as "bomb" that contains a lot of ultra-small diameter Fe3O4 nanoparticles (DOX@PFeL NPs) loaded with doxorubicin (DOX) and modified with L-valine, which can efficiently penetrate the epithelial cells via PePT1 receptor mediated endocytosis. The outer shell of this "cluster bomb" is a layer of pH-sensitive polymer (Eudragit (R) L100) that can be served as a pH-responsive switch and effectively control the "bomb" release in the intestinal microenvironment to improve the antitumor efficiency by the Fenton like reaction of DOX and Fe2+/Fe3+. This study demonstrates that the "cluster comb" oral drug delivery system can sequentially overcome the multiple biological barriers, providing a safe and effective approach for tumor therapy. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.