Silver/silver chloride nanoparticles inhibit the proliferation of human glioblastoma cells
- 161 Downloads
Glioblastomas (GBM) are aggressive brain tumors with very poor prognosis. While silver nanoparticles represent a potential new strategy for anticancer therapy, the silver/silver chloride nanoparticles (Ag/AgCl-NPs) have microbicidal activity, but had not been tested against tumor cells. Here, we analyzed the effect of biogenically produced Ag/AgCl-NPs (from yeast cultures) on the proliferation of GBM02 glioblastoma cells (and of human astrocytes) by automated, image-based high-content analysis (HCA). We compared the effect of 0.1–5.0 µg mL−1 Ag/AgCl-NPs with that of 9.7–48.5 µg mL−1 temozolomide (TMZ, chemotherapy drug currently used to treat glioblastomas), alone or in combination. At higher concentrations, Ag/AgCl-NPs inhibited GBM02 proliferation more effectively than TMZ (up to 82 and 62% inhibition, respectively), while the opposite occurred at lower concentrations (up to 23 and 53% inhibition, for Ag/AgCl-NPs and TMZ, respectively). The combined treatment (Ag/AgCl-NPs + TMZ) inhibited GBM02 proliferation by 54–83%. Ag/AgCl-NPs had a reduced effect on astrocyte proliferation compared with TMZ, and Ag/AgCl-NPs + TMZ inhibited astrocyte proliferation by 5–42%. The growth rate and population doubling time analyses confirmed that treatment with Ag/AgCl-NPs was more effective against GBM02 cells than TMZ (~ 67-fold), and less aggressive to astrocytes, while Ag/AgCl-NP + TMZ treatment was no more effective against GBM02 cells than Ag/AgCl-NPs monotherapy. Taken together, our data indicate that 2.5 µg mL−1 Ag/AgCl-NPs represents the safest dose tested here, which affects GBM02 proliferation, with limited effect on astrocytes. Our findings show that HCA is a useful approach to evaluate the antiproliferative effect of nanoparticles against tumor cells.
KeywordsCancer Glioblastoma Antiproliferative effect Metallic nanoparticles Silver/silver chloride nanoparticles High-content analysis
This work was supported by the National Council for Scientific and Technological Development (CNPq), the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Coordination for the Improvement of Higher Education Personnel (CAPES).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- Diniz LP, Almeida JC, Tortelli V et al (2012) Astrocyte-induced synaptogenesis is mediated by transforming growth factor β signaling through modulation of d-serine levels in cerebral cortex neurons. J Biol Chem 287:41432–41445. https://doi.org/10.1074/jbc.M112.380824 CrossRefPubMedPubMedCentralGoogle Scholar
- Goldlust SA, Turner GM, Goren JF (2008) Glioblastoma multiforme: multidisciplinary care and advances in therapy. Hosp Physician 1:9–23Google Scholar
- Jain P, Aggarwal V (2012) Synthesis, characterization and antimicrobial effects of silver nanoparticles from microorganisms—a review. Int J Nano Mater Sci 1:108–120Google Scholar
- Kang Y, Jung J-Y, Cho D et al (2016) Antimicrobial silver chloride nanoparticles stabilized with chitosan oligomer for the healing of burns. Materials 9:pii:E215. https://doi.org/10.3390/ma9040215
- Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466. https://doi.org/10.1016/S1470-2045(09)70025-7 CrossRefPubMedGoogle Scholar