Final Report Summary - GLIOMADDS (Development of tumor penetrating peptides for glioma targeting)
GliomaDDS project was designed to develop novel strategies to deliver antitumor drugs into solid tumors, especially to deadly brain cancer glioblastoma. The project stems from our discovery of C-end Rule (CendR) tumor penetrating peptides (TPP) that can be used to deliver more anticancer drugs to cancer tissue and enhance their penetration.
With the support of the GliomaDDS project, we characterized the CendR pathway and developed tools and technologies to identify, validate, and pre-clinically advance novel TPPs. Our functional cell-based screens to dissect the CendR cell- and tissue penetration pathway showed that neuropilin-1 binding CendR peptides are internalized in cells using an unconventional nutrient-regulated endocytosis pathway. We developed next generation sequencing-based and bioinformatics tools for improved screening of homing peptides using in vivo peptide phage display. To assess the homing profiles of the newly identified peptides we set up an isotopically-barcoded nanocarrier system to allow ultrasensitive ratiometric auditioning of homing peptide receptor status on cultured tumor cells and in live animals. Validated tumor-selective peptides were used for functionalization of drug-loaded nanoparticles of different classes to assess the effect of targeting on the drug efficacy in mouse models of glioma and various epithelial tumors.
The GliomaDDS project was instrumental for establishing a state –of-the-art cancer research and drug delivery systems laboratory at the University of Tartu, Estonia. The research contributed a panel of tumor homing ligands that is undergoing further preclinical development.
With the support of the GliomaDDS project, we characterized the CendR pathway and developed tools and technologies to identify, validate, and pre-clinically advance novel TPPs. Our functional cell-based screens to dissect the CendR cell- and tissue penetration pathway showed that neuropilin-1 binding CendR peptides are internalized in cells using an unconventional nutrient-regulated endocytosis pathway. We developed next generation sequencing-based and bioinformatics tools for improved screening of homing peptides using in vivo peptide phage display. To assess the homing profiles of the newly identified peptides we set up an isotopically-barcoded nanocarrier system to allow ultrasensitive ratiometric auditioning of homing peptide receptor status on cultured tumor cells and in live animals. Validated tumor-selective peptides were used for functionalization of drug-loaded nanoparticles of different classes to assess the effect of targeting on the drug efficacy in mouse models of glioma and various epithelial tumors.
The GliomaDDS project was instrumental for establishing a state –of-the-art cancer research and drug delivery systems laboratory at the University of Tartu, Estonia. The research contributed a panel of tumor homing ligands that is undergoing further preclinical development.