Distribution and diffusion of nanoparticles in tumoral tissue
Abraham Domb, Ph.D., from Hebrew University will work in the laboratory of Jacob Berlin, Ph.D., to investigate ways to enhance the permeability of drugs into the ‘deep’ parts of solid tumors. Efficiency of anti-cancer drug delivery to solid tumors is low, and less than 5% of drugs accumulate in the tumor following systemic administration. Direct (focal) delivery of the drug delivery systems (DDSs) into the tumor has been proposed for higher exposure of the cancer cells to the drug. Unfortunately, even clinically approved focal DDSs lead to limited intratumoral distribution of the drug (therapeutic penetration depth of only 1-2 mm) that compromises their clinical effectiveness. The team will generate and characterize new DDSs based on pasty polymers for intratumoral delivery and will investigate the ways to enhance their intratumoral distribution using orthotropic breast cancer model in experimental mice and state-of-the-art imaging-based approaches. The outcomes of this project will contribute to further understanding the mechanisms of intratumoral drug/DDSs distribution and the major factors that limit the drug/DDS permeability to the ‘deep’ parts of tumors. Furthermore, based on the experimental outcomes, formulations and strategies for efficient drug delivery and enhanced anti-cancer efficiency will be identified and recommended for clinical application.