Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles

Sci Rep. 2022 Jul 15;12(1):12078. doi: 10.1038/s41598-022-15244-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Glioblastoma* / pathology
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / pharmacology
  • Nanoparticles*
  • Polymers / pharmacology
  • Zebrafish / metabolism

Substances

  • CD44 protein, human
  • Hyaluronan Receptors
  • Polymers
  • Hyaluronic Acid

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