(175ag) Non-Targeted and Targeted Lipid Drug-Loaded Nanoparticle Combination Delivery Outperforms Either Component in Metastatic Ovarian Cancer Treatment

Metastatic ovarian cancer is a highly deadly type, primarily due to late detection and the limited efficacy of standard-of-care chemotherapies to metastatic tumors and non-adherent cancer cells. Here, we report a new strategy where a new approach that combines targeted (TLNP) and non-targeted (LNP) liposomal nanoparticles to administer novel tubulin inhibitor prodrug to treat metastatic ovarian cancer in a syngeneic mouse model. Stem-like cancer cells are a subpopulation of cancer cells that are the most aggressive with the highest potential for metastasis. These cells display a cell-membrane bound stem-cell marker on their surfaces, making this stem-cell marker an optimal target for selective delivery of nanoparticles to metastatic ovarian cancer. The treatment using a combination of LNP+TLNP formulations reduced tumor burden by 15-fold, compared to untreated control. Increased T cell and macrophage levels in treated groups also suggested antitumor immune system involvement. The LNP and TLNP components functioned synergistically through two proposed mechanisms of action. The TLNPs targeted non-adherent cancer cells in the peritoneal cavity, preventing the formation of new solid tumors, while the LNPs passively targeted existing solid tumor sites, providing a sustained release of the drug to the tumor microenvironment. At the end of treatment, half of the animals in the combination group were effectively completely cured of the metastatic ovarian cancer, while the other half had residual cancer burden.