Borrelidin is an inhibitor of threonyl-tRNA synthetase with both anticancer and antiangiogenic activities. Although borrelidin could be a potent drug that can treat metastatic cancer through synergistic therapeutic effects, its severe liver toxicity has limited the use for cancer therapeutics. In this study, we developed a liposomal formulation of borrelidin to treat metastatic breast cancer effectively through its combined anticancer and antiangiogenic effects while reducing the potential liver toxicity. The liposomal formulation was optimized to maximize loading stability and efficiency of lipophilic borrelidin in the liposomal membrane and its delivery efficiency to primary tumor in a mouse model of metastatic breast cancer. Liposomal borrelidin showed significant in vitro therapeutic effects on proliferation and migration of tumor cells and angiogenesis of endothelial cells. Furthermore, liposomal borrelidin exhibited superior inhibitory effects on primary tumor growth and lung metastasis in vivo compared to free borrelidin. More importantly, liposomal borrelidin did not induce any significant systemic toxicity in the mouse model after multiple injections.
Bibliographical noteFunding Information:
Funding information This work was supported by the Global Frontier Project (Grant No. NRF-M3A6A4-2010-0029785) through the National Research Foundation funded by the Ministry of Science, ICT & Future Planning and the Basic Science Research Program (Grant No. NRF-2017R1E1A1A01074847) through the National Research Foundation funded by the Ministry of Science and ICT, Republic of Korea.
© 2018, Controlled Release Society.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science