Using Layer-by-Layer Liposome Nanoparticles for Novel Ovarian Cancer Therapy


Dr. Lawrence B. Mensah


Mensah Lawrence B, Mohi Quadir, Stephen Morton, Jason Deng, and Paula T. Hammond

Author Affiliation: 

MIT Koch Institute


Introduction Ovarian cancer (OC) is the second most common gynaecological malignancy and the leading cause of death from gynecological cancers. Approximately 75–80% of patients present with advanced disease that is refractory to current platinum and taxol-based therapies. Though these therapies have remained a critical mainstay of disease management, the cure rate is often hampered by resistance of residual tumor. Targeted combination therapy offers a new approach in cancer treatment to target key DNA damage repair pathway molecules such as Poly (ADP-ribose) polymerase 1/2 (PARP-1/2), Breast Cancer 1/2 (BRCA1/2 ) tumor suppressor proteins, and growth factor receptor such as vascular endothelial growth factor (VEGF). These molecules perform critical roles in double stand DNA damage repair, cell proliferation, formation of tumor micro-vasculature, promote metastasis and, as a consequence are frequently dysregulated in majority of cancers.A key function of BRCA1 and BRCA2 is in dsDNA break repair via homologous recombination. BRCA1/2 mutations, which occur in most hereditary ovarian cancers and approximately 10% of all OC cases, are associated with defects in homologous recombination and genomic instability, a phenotype termed 'BRCAness‘. These cancers therefore depend heavily on PARP proteins for repair of dsDNA breaks damage. We therefore aim to treat OC with potent cytotoxicity agents such as Cisplatin to induce more dsDNA breaks in OC cells that harbor lost-of-function BRCA1/2 , while inhibiting their ability to repair the damage by blocking the function of PARP with PARP inhibitors. This will drive OC cells into apoptosis, a phenomenon referred to as ‘synthetic lethality. carry cytotoxic or anti-angiogenic agent in combination with PARP inhibitor. And the surface of liposomes decorated with moieties which selectively target OC cells and effectively deliver payloads that target multiple cellular signalling pathways with a role in tumorigenesis and to overcome resistance to platinum-based therapy.