Liposomal Coencapsulation of Doxorubicin with Listeriolysin O Increases Potency via Subcellular Targeting
Liposomal doxorubicin is a clinically important drug formulation indicated for the treatment of several different forms of cancer. For doxorubicin to exert a therapeutic effect, it must gain access to the nucleus. However, a large proportion of the liposomal doxorubicin dose fails to work because it is sequestered within endolysosomal organelles following endocytosis of the liposomes due to the phenomenon of ion trapping. Listeriolysin O (LLO) is a pore-forming protein that can provide a mechanism for endosomal escape. The present study demonstrates that liposomal coencapsulation of doxorubicin with LLO enables a significantly larger percentage of the dose to colocalize with the nucleus compared to liposomes containing doxorubicin alone. The change in intracellular distribution resulted in a significantly more potent formulation of liposomal doxorubicin as demonstrated in both the ovarian carcinoma cell line A2780 and its doxorubicin-resistant derivative A2780ADR.
Walls, Zachary F.; Gong, Henry; and Wilson, Rebecca J.. 2016. Liposomal Coencapsulation of Doxorubicin with Listeriolysin O Increases Potency via Subcellular Targeting. Molecular Pharmaceutics. Vol.13(3). 1185-1190. https://doi.org/10.1021/acs.molpharmaceut.5b00674 PMID: 26751497 ISSN: 1543-8384