title: Toxicity of L-DOPA coated iron oxide nanoparticles in intraperitoneal delivery setting - preliminary preclinical study.
abstract: Iron oxide nanoparticles are promising candidates for theranostics in cancer, that aims to achieve in one-step precise tumor imaging by magnetic resonance, and targeted therapy through surface attached anti-cancer drugs. The aim of this study was to investigate in preclinical setting the biocompatibility of new iron oxide-based nanoparticles that were coated with L-DOPA for improved dispersion in biological media. These nanostructures (NPs) were designed for biomedical applications as contrast agents and/or drug carriers. We investigated the effect exerted in vitro by NPs and L-DOPA on the viability and proliferation of normal mouse L929 fibroblasts. NPs exhibited good biocompatibility against these cells. Moreover, L-DOPA contained in NPs sustained fibroblasts proliferation and/or limited anti-proliferative effects of naked nanoparticles. In the animal study, C57BL/6 mice were injected intraperitoneally with a single dose of NPs (approximately 125 mg/kg body weight). We followed up hematological and histological parameters for one, three and seven days after NPs administration. Results indicated that NPs possibly induced local inflammation and consequent recruitment of peripheral lymphocytes, whilst the decrease of platelet counts may reflect tissue lesions caused by NPs. The histopathological study showed mild to moderate alterations in the hepatocytes, splenic and renal cells, while the brain parenchyma only presented nonspecific congestive changes. Taken altogether, the preclinical study indicated that the new iron oxide nanoparticles coated with L-DOPA were biocompatible against fibroblasts and had a convenient toxicological profile when administered intraperitoneally in a single dose to C57BL/6 mice. Accordingly, the proposed nanostructure is a promising candidate for imaging and treating dispersed peritoneal tumors.
authors.affiliation: Department Pathology, "Victor Babes" National Institute for Research and Development in Pathology and Biomedical Sciences, Bucharest, Romania; mariacomanescu@yahoo.com.
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Comănescu
authors.forename: Mihaela Andreea
authors.initials: MA
authors.lastname: Mocanu
authors.forename: Laurenţiu
authors.initials: L
authors.lastname: Anghelache
authors.forename: Bogdan
authors.initials: B
authors.lastname: Marinescu
authors.forename: Florian
authors.initials: F
authors.lastname: Dumitrache
authors.forename: Anca Daniela
authors.initials: AD
authors.lastname: Bădoi
authors.forename: Gina
authors.initials: G
authors.lastname: Manda
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D020099:Coated Materials, Biocompatible; D003287:Contrast Media / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry*; D005347:Fibroblasts / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology; D007263:Infusions, Parenteral / Q000379:methods*; D007980:Levodopa / Q000737:chemistry*; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry; D013154:Spleen / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D004337:Drug Carriers; D005290:Ferric Compounds; C000499:ferric oxide; D007980:Levodopa