Abstract 4403: Antitumor properties of ouabain in lipid double emulsion integrated with tumor cell membrane fractions

Abstract

Abstract Cell membrane proteins such as integrins are crucial for cell-cell recognition, binding and communication, cell-stromal interaction and adhesion, tumor invasion and metastasis. It was reported that cell-size hydrophobic beads coated with tumor membrane molecules could stimulate the lymphokine activated killer (LAK) cells to release IFN-alpha and TNF-alpha, and interrupted the recognition between LAK cells and tumor cells (Chong AS, 1988, 1991). Lipid double emulsion is a convenient formulation method to integrate lipid materials, hydrophilic and hydrophobic drugs in uniformed particles to achieve combinational chemotherapy. However the nonspecific uptake of double emulsion particles in vivo limits its targeting therapeutic potential. In current study, we sought to coat double emulsion particles with tumor cell membrane fraction to mimic the tumor cell surface in order to enhance the interaction and uptake of emulsion particles into tumor cells. Canine osteosarcoma cells and lymphoma cells were chosen for this study because canine cancers develop in immunocompetent environments and share many similar features observed in human cancers, such as long periods of latency for initiation, progression and development, metastasis, acquired drug resistance and recurrence. We use ouabain as therapeutic warhead in the emulsion particles because ouabain is known to have extremely high anticancer potential at nanomolar concentration level from our previous studies. The major obstacle of applying ouabain in vivo therapy is that the therapeutic dose window of ouabain is very narrow. Therefore in an attempt to mitigate such narrow therapeutic margin of safety, ouabain was formulated in lipid double emulsion by using microfluidic synthesis method and membrane emulsification method. The double emulsion particles were further coated with osteosarcoma cell membrane fraction. Our preliminary results showed enhanced antitumor activities of ouabain in tumor cell mimic-double emulsion or nanoemulsion against canine osteosarcoma cells and lymphoma cells in vitro and in orthotopic xenograft models in vivo, suggesting a promising therapeutic benefit in canine cancer targeting therapy. Citation Format: Jun Wu, Mariele Mondala, Meng-Yin Hsieh, Eugene Roberts, Richard Ermel. Antitumor properties of ouabain in lipid double emulsion integrated with tumor cell membrane fractions. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4403. doi:10.1158/1538-7445.AM2015-4403