Abstract 4586: The Leukosome: A biomimetic liposome for the targeting of inflamed tumor vasculature

The development of targeted cancer treatments with increased therapeutic efficacy is still a major challenge in drug delivery. To date, nanoscale platforms are able to extend their circulation time and accumulate in the tumor through surface functionalization with polyethylene glycol and with antibodies, peptides or ligands directed against tumor biomarkers, respectively. Despite these modifications, the mononuclear phagocytic system efficiently clears these particles from circulation while opsonization proteins prevent the proper recognition between targeting ligands and target biomarkers. Additionally, most cancers are characterized by strong inflammation and increased affinity for circulating leukocytes. The surface of the leukocyte is enriched with transmembrane proteins that determine self-tolerance, adhesion, and negotiation of the inflamed vascular barrier. As result, leukocytes can efficiently recognize and infiltrate the tumor tissues. The Leukosome is a liposomal formulation based on leukocyte membranes able to provide biocompatibility, self-tolerance and targeting. The Leukosome was enriched with up to 82 different leukocyte membrane proteins in their intact native, active configuration with the appropriate post-translational modification and orientation. Among them, CD45 favored extended circulation time and avoided unspecific clearance, while Leukocyte Associated Function-1 facilitated the targeting to and permeability of the tumor inflamed vasculature. The Leukosome retained loading capabilities similar to current liposomal formulations but sustained the release of the chemotherapeutic drug for twice as long. The physical (size, surface charge and polydispersity index), chemical (surface composition and modification, loading and release kinetics), biochemical (protein content and stability), and biological (inhibition of particle clearance, tumor targeting, effect on the vascular barrier function) properties of the Leukosomes confirmed our ability to mimic the biological features and functions of leukocytes. Compared to unmodified liposomes, Leukosomes showed 5-fold increase in circulation time, 50-fold reduction of liver accumulation and 70-fold accumulation of the payload in breast, pancreatic and melanoma models in mouse. We believe this platform will provide a superior tool for the targeting and personalization of therapeutic intervention in cancer. Citation Format: Roberto Molinaro, Alessandro Parodi, Nima Taghipour, Brandon Brown, Dickson Kirui, Michael Evangelopoulos, Francesca Taraballi, Claudia Corbo, Ennio Tasciotti. The Leukosome: A biomimetic liposome for the targeting of inflamed tumor vasculature. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4586. doi:10.1158/1538-7445.AM2014-4586