title: Loading of Gemcitabine on chitosan magnetic nanoparticles increases the anti-cancer efficacy of the drug.
abstract: Targeted delivery of anti-cancer drugs increase the efficacy, while decreasing adverse effects. Among various delivery systems, chitosan coated iron oxide nanoparticles (CsMNPs) gained attention with their biocompatibility, biodegradability, low toxicity and targetability under magnetic field. This study aimed to increase the cellular uptake and efficacy of Gemcitabine. CsMNPs were synthesized by in situ co-precipitation and Gemcitabine was loaded onto the nanoparticles. Nanoparticle characterization was performed by TEM, FTIR, XPS, and zeta potential. Gemcitabine release and stability was analyzed. The cellular uptake was shown. Cytotoxicity of free-Gemcitabine and Gem-CsMNPs were examined on SKBR and MCF-7 breast cancer cells by XTT assay. Gemcitabine loading was optimized as 30µM by spectrophotometric analyses. Drug release was highest (65%) at pH 4.2, while it was 8% at pH 7.2. This is a desired release characteristic since pH of tumor-tissue and endosomes are acidic, while the blood-stream and healthy-tissues are neutral. Peaks reflecting the presence of Gemcitabine were observed in FTIR and XPS. At neutral pH, zeta potential increased after Gemcitabine loading. TEM images displayed, Gem-CsMNPs were 4nm with uniform size-distribution and have spherical shape. The cellular uptake and targetability of CsMNPs was studied on MCF-7 breast cancer cell lines. IC50 value of Gem-CsMNPs was 1.4 fold and 2.6 fold lower than free-Gem on SKBR-3 and MCF-7 cell lines respectively, indicating the increased efficacy of Gemcitabine when loaded onto nanoparticles. Targetability by magnetic field, stability, size distribution, cellular uptake and toxicity characteristics of CsMNPs in this study provides a useful targeted delivery system for Gemcitabine in cancer therapy.
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey. Electronic address: smaryamparsian@gmail.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Parsian
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey. Electronic address: gozdeunsoy@hotmail.com.
authors.forename: Gozde
authors.initials: G
authors.lastname: Unsoy
authors.affiliation: Central Laboratory, Molecular Biology and Biotechnology R&D Center, Middle East Technical University, Ankara, Turkey.
authors.forename: Pelin
authors.initials: P
authors.lastname: Mutlu
authors.affiliation: Department of Food Engineering, Ahi Evran University, Kırşehir, Turkey.
authors.forename: Serap
authors.initials: S
authors.lastname: Yalcin
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey; Department of Engineering Sciences, Middle East Technical University, Ankara, Turkey.
authors.forename: Aysen
authors.initials: A
authors.lastname: Tezcaner
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey; Department of Biological Sciences, Middle East Technical University, Ankara, Turkey. Electronic address: ufukg@metu.edu.tr.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Gunduz
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D065546:Drug Liberation; D006801:Humans; D061986:MCF-7 Cells; D060526:Magnetic Fields; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D003841:Deoxycytidine; D048271:Chitosan; D000093542:Gemcitabine
keywords: Breast cancer; Chitosan; Gemcitabine; Magnetic nanoparticles; Targeted drug delivery