Title
Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles
Document Type
Article
Publication Date
12-1-2022
Publication Title
Scientific Reports
Volume
12
Issue
1
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.
DOI
10.1038/s41598-022-15244-0
E-ISSN
20452322
Recommended Citation
Lubanska, Dorota; Alrashed, Sami; Mason, Gage T.; Nadeem, Fatima; Awada, Angela; DiPasquale, Mitchell; Sorge, Alexandra; Malik, Aleena; Kojic, Monika; Soliman, Mohamed A.R.; deCarvalho, Ana C.; Shamisa, Abdalla; Kulkarni, Swati; Marquardt, Drew; Porter, Lisa A.; and Rondeau-Gagné, Simon. (2022). Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles. Scientific Reports, 12 (1).
https://scholar.uwindsor.ca/chemistrybiochemistrypub/282
PubMed ID
35840697