Impairing proliferation of glioblastoma multiforme with CD44+ selective conjugated polymer nanoparticles.
Sci Rep
; 12(1): 12078, 2022 07 15.
Article
en En
| MEDLINE
| ID: mdl-35840697
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glioblastoma
/
Nanopartículas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá