Poly(allylguanidine)-Coated Surfaces Regulate TGF-β in Glioblastoma Cells to Induce Apoptosis via NF-κB Pathway Activation

ACS Appl Mater Interfaces. 2021 Dec 15;13(49):59400-59410. doi: 10.1021/acsami.1c21027. Epub 2021 Nov 30.

Abstract

Polycationic biomaterials are currently widely applied in neuronal cell cultures to promote cell adhesion and viability. However, polycations generally have cytotoxic properties that limit their application in the field of biomaterials. In this study, we examined the use of a novel polycation poly(allylguanidine) (PAG), which contains a guanidine group in the side chain and a structure similar to poly(allylamine hydrochloride) (PAH), an example of another commonly used polycation. Our findings showed that exposure to PAG induced apoptosis in glioblastoma (GBM) cells, while exposure to PAH induced necrosis. Compared to control groups, the PAG coating significantly limited the proliferation of GBM8901 in vitro and in vivo. Furthermore, GBM8901 cells exposed to the PAG coating exhibited increased levels of phospho-p65 and phosphor-IκB, implying that GBM8901 cells underwent apoptotic cell death via the NF-κB pathway by the regulation of TGF-β. This result was further confirmed to be consistent with the experimental results from western blot protein analysis and apoptosis/necrosis assays. These findings indicate that the polycation PAG has the potential to not only suppress the proliferation of GBM8901 cancer cells but also improve the neural viability and promote the differentiation of neural stem/precursor cells into mature neurons. In conclusion, biomaterials such as PAG act as extremely potent options for applications in the treatment of pathological conditions such as brain cancer.

Keywords: NF-κB pathway; apoptosis; glioblastoma; poly(allylguanidine) (PAG); polycation.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Coated Materials, Biocompatible / chemistry
  • Coated Materials, Biocompatible / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Guanidine / chemistry
  • Guanidine / pharmacology*
  • Humans
  • Materials Testing
  • NF-kappa B / metabolism*
  • Polymers / chemistry
  • Polymers / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Coated Materials, Biocompatible
  • NF-kappa B
  • Polymers
  • Guanidine