Faculty, Staff and Student Publications
Publication Date
7-15-2022
Journal
Scientific Reports
Abstract
Glioblastoma is one of the most aggressive types of cancer with success of therapy being 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-based Conjugated Polymer Nanoparticles (CPNs) with an average diameter of 109 nm. CPNs 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 regulated the levels and signaling activity of the CD44 receptor, decreasing stemness, invasive properties and proliferation of the CD44-TIC populations in vitro and in a patient-derived xenograft zebrafish model. This work proposes a novel, CPN- based, and surface moiety-driven selective way of targeting of TIC populations in brain cancer.
Keywords
Biotechnology, Cancer, Neuroscience, Chemistry, Materials science, Nanoscience and technology
DOI
10.1038/s41598-022-15244-0
PMID
35840697
PMCID
PMC9287456
PubMedCentral® Posted Date
July 2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Comments
Supplementary Materials
PMID: 35840697