Abstract 3910: Biomimetic proteo-lipid vesicles for the treatment of melanoma

Abstract

Abstract The systemic administration of pharmaceutics presents several drawbacks, such as: i) reduced drug's stability because of the degradation by lytic enzymes in pathological (secreted by the cancer cells) or physiologic (lysosome acidic environment) conditions, and ii) lack of specific tumor targeting, that requires high doses to achieve therapeutically effective drug concentrations, and increases the risk of off-target effects. Drug encapsulation and delivery through nanocarriers can offer many advantages over free drugs, as prevention of drug degradation, control of drug pharmacokinetic and biodistribution, and improvement of intracellular penetration, as well as drug solubilization. However, regardless of the type of approach, the organs of the mononuclear phagocytic system efficiently clear the particles from circulation while protein opsonization often prevents the proper interaction between targeting ligands and target biomarkers. Most cancers are characterized by inflammation and increased leukocyte infiltration. The surface of the leukocyte, in fact, is enriched with transmembrane proteins that determine self-tolerance, adhesion, and negotiation of the inflamed vascular barrier. Leveraging on leukocyte ability to efficiently recognize and infiltrate the tumor tissues, we developed a liposome-like Biomimetic Vesicle (BioV), formulated with leukocyte membrane proteins able to provide extended biocompatibility, self-tolerance and targeting. We hypothesize that the transferring of leukocyte membrane proteins on the surface on a nanovesicle will enhance BioV selective targeting towards the tumor-associated vasculature, increase payload's accumulation, and improve cancer specific cytotoxicity. C57BL mice were intradermally injected with B16 cells. Intravital microscopy and typical tumor growth inhibition curve associated with histological analysis were used to assess BioV targeting and efficacy, respectively in comparison with conventional liposomes and free drug. Once the tumor reached 70-100 mm3, mice were randomly divided into 6 groups (n = 10) and treated with saline (CTRL), free doxorubicin (DOX), empty and DOX-loaded liposomes, empty and DOX-loaded BioVs, at a drug concentration of 7 mg/Kg. Melanoma-bearing mice were treated once per week for one month, and tumor volume and survival rate were investigated. Compared to the other groups, BioVs showed higher tumor targeting and DOX accumulation, increased antitumor efficacy, and prolonged survival rate. Histological analysis on tumor slides showed increased apoptosis and reduced immune cell infiltration in the groups treated with BioVs. We believe that BioV represents a promising drug delivery system possessing advantageous biomimetic properties. The high versatility of this approach and its molecular mechanisms of action make this platform a technology applicable for the treatment of all the inflammation-related cancers. Citation Format: Roberto Molinaro, Jonathan Otto Martinez, Claudia Corbo, Naama E. Toledano Furman, Enrica De Rosa, Alessandro Parodi, Ennio Tasciotti. Biomimetic proteo-lipid vesicles for the treatment of melanoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3910.