Transferrin-targeted nanoparticles containing zoledronic acid as a potential tool to inhibit glioblastoma growth

G. Salzano, S. Zappavigna, A. Luce, N. D'Onofrio, M. L. Balestrieri, A. Grimaldi, S. Lusa, D. Ingrosso, S. Artuso, Manuela Porru, C. Leonetti, M. Caraglia, G. De Rosa

Research output: Contribution to journalArticle

Abstract

The treatment of glioblastoma (GBM) is a challenge for the biomedical research since cures remain elusive. Its current therapy, consisted on surgery, radiotherapy, and concomitant chemotherapy with temozolomide (TMZ), is often uneffective. Here, we proposed the use of zoledronic acid (ZOL) as a potential agent for the treatment of GBM. Our group previously developed self-assembling nanoparticles, also named PLCaPZ NPs, to use ZOL in the treatment of prostate cancer. Here, we updated the previously developed nanoparticles (NPs) by designing transferrin (Tf)-targeted selfassembling NPs, also named Tf-PLCaPZ NPs, to use ZOL in the treatment of brain tumors, e.g., GBM. The efficacy of Tf-PLCaPZ NPs was evaluated in different GBM cell lines and in an animal model of GBM, in comparison with PLCaPZ NPs and free ZOL. Tf-PLCaPZ NPs were characterized by a narrow size distribution and a high incorporation efficiency of ZOL. Moreover, the presence of Tf significantly reduced the hemolytic activity of the formulation. In vitro, in LN229 cells, a significant uptake and cell growth inhibition after treatment with Tf-PLCaPZ NPs was achieved. Moreover, the sequential therapy of TMZ and Tf-PLCaPZ NPs lead to a superior therapeutic activity compared to their single administration. The results obtained in mice xenografted with U373MG, revealed a significant anticancer activity of Tf-PLCaPZ NPs, while the tumors remained unaffected with free TMZ. These promising results introduce a novel type of easy-to-obtain NPs for the delivery of ZOL in the treatment of GBM tumors.

Original languageEnglish
Pages (from-to)811-830
Number of pages20
JournalJournal of Biomedical Nanotechnology
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Keywords

  • Glioblastoma
  • Self-Assembling Nanoparticles
  • Temozolomide
  • Transferrin
  • Zoledronic Acid

ASJC Scopus subject areas

  • Materials Science(all)
  • Bioengineering
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Pharmaceutical Science

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  • Cite this

    Salzano, G., Zappavigna, S., Luce, A., D'Onofrio, N., Balestrieri, M. L., Grimaldi, A., Lusa, S., Ingrosso, D., Artuso, S., Porru, M., Leonetti, C., Caraglia, M., & De Rosa, G. (2016). Transferrin-targeted nanoparticles containing zoledronic acid as a potential tool to inhibit glioblastoma growth. Journal of Biomedical Nanotechnology, 12(4), 811-830. https://doi.org/10.1166/jbn.2016.2214