title: Selective in vitro anticancer effect of superparamagnetic iron oxide nanoparticles loaded in hyaluronan polymeric micelles.
abstract: Due to its native origin, excellent biocompatibility and biodegradability, hyaluronan (HA) represents an attractive polymer for superparamagnetic iron oxide nanoparticles (SPION) coating. Herein, we report HA polymeric micelles encapsulating oleic acid coated SPIONs, having a hydrodynamic size of about 100 nm and SPION loading capacity of 1-2 wt %. The HA-SPION polymeric micelles were found to be selectively cytotoxic toward a number of human cancer cell lines, mainly those of colon adenocarcinoma (HT-29). The selective inhibition of cell growth was even observed when the SPION loaded HA polymeric micelles were incubated with a mixture of control and cancer cells. The selective in vitro inhibition could not be connected with an enhanced CD44 uptake or radical oxygen species formation and was rather connected with a different way of SPION intracellular release. While aggregated iron particles were visualized in control cells, nonaggregated solubilized iron oxide particles were detected in cancer cells. In vivo SPION accumulation in intramuscular tumor following an intravenous micelle administration was confirmed by magnetic resonance (MR) imaging and histological analysis. Having a suitable hydrodynamic size, high magnetic relaxivity, and being cancer specific and able to accumulate in vivo in tumors, SPION-loaded HA micelles represent a promising platform for theranostic applications.
authors.affiliation: Contipro Pharma, Dolní Dobrouč 401, 561 02 Dolní Dobrouč, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Smejkalová
authors.forename: Kristina
authors.initials: K
authors.lastname: Nešporová
authors.forename: Gloria
authors.initials: G
authors.lastname: Huerta-Angeles
authors.forename: Jakub
authors.initials: J
authors.lastname: Syrovátka
authors.forename: Daniel
authors.initials: D
authors.lastname: Jirák
authors.forename: Andrea
authors.initials: A
authors.lastname: Gálisová
authors.forename: Vladimír
authors.initials: V
authors.lastname: Velebný
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D018938:Caco-2 Cells; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000737:chemistry; D045325:HCT116 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry; D061986:MCF-7 Cells; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008823:Micelles; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D041701:Swiss 3T3 Cells; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D008823:Micelles; D011108:Polymers; C000499:ferric oxide; D006820:Hyaluronic Acid