Medical treatment of orthotopic glioblastoma with transferrin conjugated nanoparticles encapsulating zoledronic acid

Manuela Porru, Silvia Zappavigna, Giuseppina Salzano, Amalia Luce, Antonella Stoppacciaro, Maria Luisa Balestrieri, Simona Artuso, Sara Lusa, Giuseppe De Rosa, Carlo Leonetti, Michele Caraglia

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastomas are highly aggressive adult brain tumors with poor clinical outcome. In the central nervous system (CNS) the blood-brain barrier (BBB) is the most important limiting factor for both development of new drugs and drug delivery. Here, we propose a new strategy to treat glioblastoma based on transferrin (Tf)- targeted self-assembled nanoparticles (NPs) incorporating zoledronic acid (ZOL) (NPs-ZOL-Tf). NPs-ZOL-Tf have been assessed on the glioblastoma cell line U373MGLUC that showed a refractoriness in vitro to temozolomide (TMZ) and fotemustine (FTM). NPs-ZOL-Tf treatment resulted in higher in vitro cytotoxic activity than free ZOL. However, the potentiation of anti-proliferative activity of NPs-ZOL-Tf was superimposable to that one induced by NPs-ZOL (not armed with Tf). On the other hand, NPs-ZOL-Tf showed a higher antitumor efficacy if compared with that one caused by NPs-ZOL in immunosuppressed mice intramuscularly bearing U373MG-LUC xenografts, inducing a significant tumor weight inhibition (TWI). The experiments performed on mice with intracranial U373MG-LUC xenografts confirmed the efficacy of NPs-ZOL-Tf. These effects were paralleled by a higher intratumour localization of fluorescently-labeled-NPs-Tf both in intramuscular and intracranial xenografts. In conclusion, our results demonstrate that the encapsulation of ZOL increases the antitumor efficacy of this drug in glioblastoma through the acquisition of ability to cross the BBB.

Original languageEnglish
Pages (from-to)10446-10459
Number of pages14
JournalOncotarget
Volume5
Issue number21
Publication statusPublished - 2014

Keywords

  • Calcium phosphate self-assembly nanoparticles
  • Delivery
  • Glioblastoma
  • Intracranial xenografts
  • Transferrin
  • Zoledronic acid

ASJC Scopus subject areas

  • Oncology

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