title: Chitosan magnetic nanoparticles for pH responsive Bortezomib release in cancer therapy.
abstract: The use of nanotechnology in cancer treatment offers exciting opportunities, including the possibility of destroying tumors with minimal damage to healthy tissue by novel targeted drug delivery systems. pH differences between healthy and tumor microenvironment provide pH responsive release of drugs at tumor site via smart nanoparticles. In this study, chitosan coated superparamagnetic iron oxide nanoparticles (CS MNPs) were in situ synthesized by ionic crosslinking method as nanocarrier systems and loaded with the drug Bortezomib (Velcade(®)). The drug loading capacity, drug release and stability of CS MNPs were analyzed. CS MNPs were visualized inside the cells by fluorescence microscopy. The cytotoxicity of Bortezomib, CS MNPs and Bortezomib loaded CS MNPs were tested by XTT analyses in vitro. Gene expression analyses revealed that pro-apoptotic PUMA and NOXA genes were upregulated while anti-apoptotic BCL-2, SURVIVIN and cIAP-2 genes were downregulated at Bortezomib loaded CS MNP treated cells. Immunocytochemical analyses demonstrated an increase in p53 tumor suppressor protein levels at treated cells, which supports the upregulation of PUMA and NOXA genes, while Survivin protein level did not significantly change. This study points out that the pH responsive magnetic targeting of Bortezomib is more efficacious than free drug treatment. Moreover, targeted delivery of Bortezomib would reduce the frequency of drug administration by lowering the required amount of drug dose.
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: 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.
authors.forename: Rouhollah
authors.initials: R
authors.lastname: Khodadust
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 Pathology, Gülhane Military Medical Academy, Ankara, Turkey.
authors.forename: Onder
authors.initials: O
authors.lastname: Onguru
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, Turkey. Electronic address: ufukg@metu.edu.tr.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Gunduz
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000069286:Bortezomib / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D004705:Endocytosis / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D058185:Magnetite Nanoparticles; D000069286:Bortezomib; D048271:Chitosan
keywords: Bortezomib; Chitosan; Magnetic nanoparticles; Targeted drug delivery