Novel lipid-based nanoparticles containing saponins for targeted delivery and enhanced efficacy of chemotherapeutics in neuroblastoma

• Applicant: Dr. Roger Gilabert-Oriol
• Subject Area: Pharmacy
• Term: from 2015 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 276307910

Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system that represents the most common solid tumor of infancy. Despite intensification of therapy, 5-year event free survival remains less than 50% in patients with unfavorable prognostic markers and new treatment strategies must be considered for this young patient population. This proposal will focus in developing novel strategies to increase the efficacy of chemotherapeutic agents specifically delivered to NB cells. Therefore, chemotherapeutics such as topotecan will be loaded into lipid-based nanoparticles (LNPs) and their intracellular delivery will be enhanced by saponins (plant secondary metabolites). LNPs that will be prepared are novel because of the fact that incorporation of saponins into liposomal formulations has not been attempted yet. LNPs will be characterized by physicochemical methods, drug release and stability assay. The enhancement of intracellular drug delivery by saponins will be confirmed by cytotoxicity, apoptosis, autophagy assay and imaging techniques. The most efficient LNP formulations will be targeted to GD2 (surface glycolipid antigen over-expressed in NB) by post-insertion of anti-GD2 antibody. Targeted LNPs will be characterized for their binding specificity and their ability to interact with the innate immune system. The optimized targeted LNP formulation will be further investigated in vivo for its acute toxicity, pharmacokinetics and anti-tumor efficacy in a xenograft mouse model. It is expected that the developed targeted LNPs will augment the efficacy of delivered drug in target NB cells and improve the drug accumulation in the tumor.The targeted LNPs developed in this project present a great therapeutic potential to establish a new platform technology for tumor therapy.

• DFG Programme: Research Fellowships
• International Connection: Canada
• Host: Professor Dr. Marcel Bally