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Antitumor effect of novel gallium compounds and efficacy of nanoparticle-mediated gallium delivery in lung cancer.

Abstract
The widespread application of gallium (Ga) in cancer therapy has been greatly hampered by lack of specificity resulting in poor tumor accumulation and retention. To address the challenge, two lipophilic gallium (III) compounds (gallium hexanedione; GaH and gallium acetylacetonate; GaAcAc) were synthesized and antitumor studies were conducted in human lung adenocarcinoma (A549) cells. Nanoparticles (NPs) containing various concentrations of the Ga compounds were prepared using a binary mixture of Gelucire 44/14 and cetyl alcohol as matrix materials. NPs were characterized based on size, morphology, stability and biocompatibility. Antitumor effects of free or NP-loaded Ga compounds were investigated based on cell viability, production of reactive oxygen species and reduction of mitochondrial potential. Compared to free Ga compounds, cytotoxicity of NP-loaded Ga (5-150 microg/ml) was less dependent on concentration and incubation time (exposure) with A549 cells. NP-mediated delivery (5-150 microg Ga/ml) enhanced antitumor effects of Ga compounds and the effect was pronounced at: (i) shorter incubation times; and (ii) at low concentrations of gallium (approximately 50 microg/ml) (p < 0.0006). Additional studies showed that NP-mediated Ga delivery was not dependent on transferrin receptor uptake mechanism (p > 0.13) suggesting the potential in overcoming gallium resistance in some tumors. In general, preparation of stable and biocompatible NPs that facilitated Ga tumor uptake and antitumor effects could be effective in gallium-based cancer therapy.
AuthorsDaniel Wehrung, Moses O Oyewumi
JournalJournal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 8 Issue 1 Pg. 161-71 (Feb 2012) ISSN: 1550-7033 [Print] United States
PMID22515104 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Biocompatible Materials
  • Coordination Complexes
  • Drug Carriers
  • Reactive Oxygen Species
  • Transferrin
  • Gallium
Topics
  • Antineoplastic Agents (administration & dosage, chemistry, pharmacokinetics)
  • Biocompatible Materials (administration & dosage, chemistry, pharmacokinetics)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Coordination Complexes (administration & dosage, chemistry, pharmacokinetics)
  • Drug Carriers (administration & dosage, chemistry)
  • Drug Stability
  • Endocytosis (drug effects)
  • Gallium (administration & dosage, chemistry, pharmacokinetics)
  • Hemolysis (drug effects)
  • Humans
  • Lung Neoplasms (drug therapy, metabolism)
  • Materials Testing
  • Membrane Potential, Mitochondrial (drug effects)
  • Nanoparticles (administration & dosage, chemistry)
  • Particle Size
  • Platelet Aggregation (drug effects)
  • Reactive Oxygen Species (metabolism)
  • Transferrin (chemistry, pharmacology)

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