Impairing Proliferation of Glioblastoma Multiforme with CD44+ Selective Conjugated Polymer Nanoparticles

Abstract

Glioblastoma is one of the most aggressive types of cancer with median survival of only 15 months. Successful therapy is hampered by the existence of treatment resistant populations of stem-like tumour initiating cells (TICs) and poor blood-brain barrier drug penetration. Therapies capable of effectively targeting the TIC population are in high demand. Here, we synthesize spherical diketopyrrolopyrrole (DPP)-based conjugated polymer nanoparticles (CPNs) with an average diameter of 109 nm. The CPN were designed to include fluorescein-conjugated hyaluronic acid (HA), a ligand for the CD44 receptor present on one population of TICs. We demonstrate blood-brain barrier permeability of this system and concentration and cell cycle phase-dependent selective uptake of HA-CPNs in CD44 positive GBM-patient derived cultures. Interestingly, we found that uptake alone decreases stemness, invasive properties and proliferation of the CD44-TIC population in zebrafish PDX models in vivo. This study is the first to show surface moiety-driven selectivity of conjugated polymer nanoparticles in targeting TIC populations in brain cancer.