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Antitumor Effect of Novel Gallium Compounds and Efficacy of Nanoparticle-Mediated Gallium Delivery in Lung Cancer

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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 μg/ml) was less dependent on concentration and incubation time (exposure) with A549 cells. NP-mediated delivery (5–150 μg 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 (∼50 μg/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.

Keywords: BIOCOMPATIBILITY; CYTOTOXICITY; GALLIUM ACETYLACETONATE; GALLIUM HEXANEDIONE; HUMAN LUNG ADENOCARCINOMA CELLS; NANOPARTICLES

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jbn.2012.1361

Publication date: February 1, 2012

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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