title: In vitro hematological and in vivo immunotoxicity assessment of dextran stabilized iron oxide nanoparticles.
abstract: Iron oxide nanoparticles have attracted enormous interest as potential therapeutic agents. The purpose of this study was to examine the in vitro hematological toxicity and in vivo immune response toward previously synthesized and characterized dextran stabilized iron oxide nanoparticles (DIONPs) developed for hyperthermia application. Peripheral whole blood from human volunteers was used to investigate hemolysis, platelet aggregation, lymphocyte proliferation and cytokine mRNA expression induced by DIONPs in vitro. In the concentration range of 0.008-1 mg/ml, DIONPs did not induce relevant levels of hemolysis or platelet aggregation. Assessment of lymphocyte function showed significant suppression of the proliferation activity of T-lymphocytes in cultures stimulated with the mitogen phytohemagglutinin (PHA). In addition, inhibition of PHA-induced cytokine mRNA expressions was also seen. However, systemic administration of DIONPs resulted in enhanced proliferation of mitogen-stimulated spleen derived lymphocytes and secretion of IL-1β at day 7 post exposure. In conclusion, our results demonstrate that immune response is influenced variably by nanoparticles and its degradation milieu. Further investigation of the observed immunosuppressive effects of DIONPs in immune stimulated animal models is required to assess the functional impact of such a response.
authors.affiliation: Division of Toxicology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojapura, Thiruvananthapuram 695 012, Kerala, India.
authors.forename: Sheeja Liza
authors.initials: SL
authors.lastname: Easo
authors.affiliation: Division of Toxicology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojapura, Thiruvananthapuram 695 012, Kerala, India. Electronic address: mohanpv10@gmail.com.
authors.forename: P V
authors.initials: PV
authors.lastname: Mohanan
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000235:genetics*; D003911:Dextrans / Q000737:chemistry*; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D046529:Microscopy, Electron, Transmission; D010974:Platelet Aggregation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
chemical_list: D016207:Cytokines; D003911:Dextrans; D005290:Ferric Compounds; C000499:ferric oxide
keywords: Cytokines; Hemolysis; Intravenous; Iron oxide nanoparticles; Lymphocyte proliferation; Platelet aggregation