Therapeutic efficacy of doxorubicin delivery by a CO2 generating liposomal platform in breast carcinoma

Abstract

Drug delivery using thermosensitive liposomes (TSL) has significant potential for tumor drug targeting and can be combined with local hyperthermia to trigger drug release. Although TSL-mediated drug delivery can be effective by itself, we developed doxorubicin (DOX)-containing CO2 bubble-generating TSL (TSL-C) that were found to enhance the antitumor effects of DOX owing to the synergism between burst release of drug and hyperthermia-induced CO2 generation. An ultrasound imaging system was used to monitor hyperthermia-induced CO2 generation in TSL-C and the results revealed that hyperthermia-induced CO2 generation in TSL-C led to increased DOX release compared to that observed for non-CO2-generating TSL. Moreover, TSL-C significantly inhibited the tumor growth in MDA-MB-231 tumor-bearing mice compared to TSL (p<0.004). Taken together, we demonstrated that the TSL-C platform increased the therapeutic efficacy of cancer chemotherapy and showed the applicability of this approach to increase drug release within the tumor microenvironment. As a novel and highly effective drug delivery platform, TSL-C has great potential for use in a broad range of applications for the treatment of various human diseases. Statement of SignificanceWe have developed a novel method for drug release from liposomes by gas (CO2) generation in tumor microenvironment. In addition, we demonstrate therapeutic efficacy in breast carcinoma. CO2-generated liposomal doxorubicin is a novel and highly attractive delivery system for anticancer drug with the potential for broad applications in human disease.