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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
15 07 2022
Historique:
received: 15 03 2022
accepted: 21 06 2022
entrez: 15 7 2022
pubmed: 16 7 2022
medline: 20 7 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35840697
doi: 10.1038/s41598-022-15244-0
pii: 10.1038/s41598-022-15244-0
pmc: PMC9287456
doi:

Substances chimiques

CD44 protein, human 0
Hyaluronan Receptors 0
Polymers 0
Hyaluronic Acid 9004-61-9

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

12078

Subventions

Organisme : CIHR
ID : 406811
Pays : Canada

Informations de copyright

© 2022. The Author(s).

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Auteurs

Dorota Lubanska (D)

Department of Biomedical Sciences, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Sami Alrashed (S)

Department of Biomedical Sciences, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Gage T Mason (GT)

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Fatima Nadeem (F)

Department of Biomedical Sciences, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Angela Awada (A)

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Mitchell DiPasquale (M)

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Alexandra Sorge (A)

Department of Biomedical Sciences, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Aleena Malik (A)

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Monika Kojic (M)

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Mohamed A R Soliman (MAR)

Department of Neurosurgery, Faculty of Medicine, Cairo University, Cairo, Egypt.
Department of Neurosurgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA.
Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.

Ana C deCarvalho (AC)

Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, 48202, USA.

Abdalla Shamisa (A)

Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.

Swati Kulkarni (S)

Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.

Drew Marquardt (D)

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.
Department of Physics, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada.

Lisa A Porter (LA)

Department of Biomedical Sciences, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada. lporter@uwindsor.ca.

Simon Rondeau-Gagné (S)

Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave., Windsor, ON, N9B 3P4, Canada. srondeau@uwindsor.ca.

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Classifications MeSH