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Medical treatment of orthotopic glioblastoma with transferrin-conjugated nanoparticles encapsulating zoledronic acid
- Source :
- Europe PubMed Central, Oncotarget
- Publication Year :
- 2014
- Publisher :
- Creative Commons Attribution 3.0 License., 2014.
-
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 U373MG-LUC 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.
- Subjects :
- Male
intracranial xenografts
Apoptosis
Pharmacology
Zoledronic Acid
Mice, Inbred Strain
Nitrosourea Compounds
Mice
Drug Delivery Systems
Nanoparticle
Neoplasm
chemistry.chemical_classification
Cell Growth Processe
Diphosphonates
calcium phosphate self-assembly nanoparticles
Brain Neoplasms
Imidazoles
Transferrin
Tumor Burden
Dacarbazine
medicine.anatomical_structure
Diphosphonate
Oncology
Blood-Brain Barrier
Drug delivery
delivery
Research Paper
Human
medicine.drug
Glioblastoma
zoledronic acid
transferrin
Mice, Inbred Strains
Cell Growth Processes
Nitrosourea Compound
Blood–brain barrier
Brain Neoplasm
Organophosphorus Compounds
Cell Line, Tumor
Temozolomide
medicine
Animals
Humans
Imidazole
Animal
business.industry
technology, industry, and agriculture
Apoptosi
medicine.disease
Xenograft Model Antitumor Assays
Zoledronic acid
chemistry
Drug Resistance, Neoplasm
Nanoparticles
Fotemustine
Organophosphorus Compound
business
Drug Delivery System
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Europe PubMed Central, Oncotarget
- Accession number :
- edsair.doi.dedup.....11927b862cd70b7cf9fabbfef56f7023