Co-Delivery of Chloroquine and Doxorubicin by Hypoxia-Responsive Liposomes for Enhanced Synergistic Antitumor Activity in Treating Solid Tumor

Abstract

Chloroquine, initially used to treat malaria, has been discovered as a sensitizer to augment antitumor activity of other clinically used chemotherapeutics. In this work, chloroquine and doxorubicin were co-loaded into hypoxia-responsive liposomes to synergistically treat solid tumor. In vitro drug release profiles demonstrated that the liposomes were of not only good stability under normoxic condition but also high sensitivity under hypoxic condition. In vitro cell experiments demonstrated that chloroquine augmented doxorubicin cytotoxicity, and co-loaded liposomes were thus more toxic than single-loaded liposomes, especially under hypoxic condition, as a result of hypoxia-responsive drug release. These findings highlighted the potential for chloroquine and doxorubicin co-loaded hypoxia-responsive liposomes in treating solid tumors.