title: Cytotoxic and cytostatic side effects of chitosan nanoparticles as a non-viral gene carrier.
abstract: Although chitosan nanoparticles (CNs) became a promising tool for several biological and medical applications owing to their inherent biocompatibility and biodegradability features, studies regarding their effects on cytotoxic and cytostatic properties still remain insufficient. Therefore, in the present study, we decided to perform comprehensive analysis of the interactions between CNs-pKindling-Red-Mito (pDNA) and different cell line models derived from blood system and human solid tissues cancers. The resulting CNs-pDNA was investigated in terms of their cellular uptake, transfection efficiency, and physico-chemical, cytotoxic and cytostatic properties. The nanoparticles showed high encapsulation efficiency and physical stability for various formulations even after two days time period. Moreover, high gene expression levels were observed after 96h of transfection. CNs-pDNA treatment, despite the absence of oxidative stress induction, caused cell cycle arrest in G0/G1 phase and as a consequence led to premature senescence which turned out to be both p21-dependent and p21-independent. Also, observed DNMT2 upregulation may suggest the activation of different pathways protecting from the results of CNs-mediated stress. In conclusion, treatment of different cell lines with CNs-pDNA showed that their biocompatibility was limited and the effects were cell type-dependent.
authors.affiliation: Biotechnology and Bioengineering Department, Izmir Institute of Technology, Urla, Izmir 35430, Turkey.
authors.forename: Gizem
authors.initials: G
authors.lastname: Bor
authors.affiliation: Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mytych
authors.affiliation: Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Department of Plant Physiology, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Zebrowski
authors.affiliation: Centre of Applied Biotechnology and Basic Sciences, University of Rzeszow, Werynia 502, 36-100 Kolbuszowa, Poland; Department of Genetics, University of Rzeszow, Rejtana 16C, 35-959 Rzeszow, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Wnuk
authors.affiliation: Department of Chemistry, Izmir Institute of Technology, Urla, Izmir 35430, Turkey. Electronic address: gulsahsanli@iyte.edu.tr.
authors.forename: Gülşah
authors.initials: G
authors.lastname: Şanlı-Mohamed
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D018014:Gene Transfer Techniques; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010957:Plasmids
chemical_list: C430876:FP595 protein, Anemonia sulcata; D008164:Luminescent Proteins; D004247:DNA; D048271:Chitosan
keywords: Cancer cells; Chitosan; Cytotoxicity; Gene delivery; Monocytes; Nanoparticles; pDNA