Document Type : Conference Proceedings
Authors
1
M.Sc Student of Medical Physics, Students Research Committee, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
2
Assistant Professor, Department of Medical Physics, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
3
Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
4
Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Abstract
Introduction: In recent years, bismuth-based nanomaterials have been widely used in medical researches as imaging, drug delivery and x-ray radiosensitizing agents. Due to their anti-microbial effects against Helicobacter pylori (HP), bismuth colloidal compounds are used to treat various types of diseases such as chronic gastritis. Despite their advantages, bismuth-based compounds have shown many toxic effects in humans. There are few studies on cytotoxicity effects of bismuth (ΙΙΙ) oxide (Bi2O3) nanoparticles (NPs). Based on the natural high affinity of folate for the folate receptor protein (FR), which is commonly expressed on the surface of many human cancers, folate-drug conjugates bind tightly to the FR and trigger cellular uptake via endocytosis. Therefore, we aimed to investigate the cytotoxicity effects of 5-ALA-conjugated Bi2O3 NPs, 5-ALA-folate-conjugated Bi2O3 NPs and free 5-ALA on oral squamous carcinoma cell line (KB cells) for the first time. 5-ALA is used in photo dynamic detection and photodynamic surgery of cancer. Being a precursor of a photosensitizer, 5-ALA is also used as an add on agent for photodynamic therapy.
Materials and Methods: Bi2O3 NPs were synthesized and conjugated with folate and 5- aminolevulinic acid (5-ALA). KB cells were cultured monolayer and incubated with 10, 20, 50, 100 and 200 μg/ml concentrations of free 5-ALA, 5-ALA-folate-conjugated Bi2O3 NPs and 5-ALA-conjugated Bi2O3 NPs for 24 hours. The survival of the cells obtained after 24 h of incubation with the materials using MTT assay.
Results: Bi2O3 NPs were synthesized (~20 nm) and conjugated to folate and (5-ALA). Results indicated that the significant cellular death were noted at the concentrations more than of 50 μg/ml for all compounds that cell viability reduced to 37%, 49% and 63% in groups receiving 5-ALA-folate-conjugated NPs, 5-ALA-conjugated Bi2O3 NPs and free 5-ALA, respectively. The cytotoxicity of the materials on KB cells also increased with increasing concentrations of synthesized NPs.
Conclusion:5-ALA-folate-conjugated NPs, 5-ALA-conjugated Bi2O3 NPs and free 5-ALA were easily taken up by the cells and showed cytotoxic effects at high concentrations. Folic acid conjugation facilitates selective targeting of the KB cells with the overexpression of the folate receptors and improves internalization of the drugs through receptor-mediated endocytosis
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