title: Zwitterion-Coated Iron Oxide Nanoparticles: Surface Chemistry and Intracellular Uptake by Hepatocarcinoma (HepG2) Cells.
abstract: Nanoparticles (NPs) have received much attention in recent years for their diverse potential biomedical applications. However, the synthesis of NPs with desired biodistribution and pharmacokinetics is still a major challenge, with NP size and surface chemistry being the main factors determining the behavior of NPs in vivo. Here we report on the surface chemistry and in vitro cellular uptake of magnetic iron oxide NPs coated with zwitterionic dopamine sulfonate (ZDS). ZDS-coated NPs were compared to similar iron oxide NPs coated with PEG-like 2-[2-(2-methoxyethoxy)ethoxy]acetic acid (MEEA) to investigate how surface chemistry affects their in vitro behavior. ZDS-coated NPs had a very dense coating, guaranteeing high colloidal stability in several aqueous media and negligible interaction with proteins. Treatment of HepG2 cells with increasing doses (2.5-100 μg Fe/mL) of ZDS-coated iron oxide NPs had no effect on cell viability and resulted in a low, dose-dependent NP uptake, inferior than most reported data for the internalization of iron oxide NPs by HepG2 cells. MEEA-coated NPs were scarcely stable and formed micrometer-sized aggregates in aqueous media. They decreased cell viability for dose ≥50 μg Fe/mL, and were more efficiently internalized than ZDS-coated NPs. In conclusion, our data indicate that the ZDS layer prevented both aggregation and sedimentation of iron oxide NPs and formed a biocompatible coating that did not display any biocorona effect. The very low cellular uptake of ZDS-coated iron NPs can be useful to achieve highly selective targeting upon specific functionalization.
authors.affiliation: †Laboratorio di Nanotecnologie, Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via G. Fantoli 16/15, 20138 Milano, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mondini
authors.affiliation: ‡Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, via L. Vanvitelli 32, 20133 Milano, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Leonzino
authors.affiliation: †Laboratorio di Nanotecnologie, Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via G. Fantoli 16/15, 20138 Milano, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Drago
authors.affiliation: †Laboratorio di Nanotecnologie, Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via G. Fantoli 16/15, 20138 Milano, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Ferretti
authors.affiliation: †Laboratorio di Nanotecnologie, Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via G. Fantoli 16/15, 20138 Milano, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Usseglio
authors.affiliation: §Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Maggioni
authors.affiliation: ‡Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, via L. Vanvitelli 32, 20133 Milano, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tornese
authors.affiliation: ‡Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, via L. Vanvitelli 32, 20133 Milano, Italy.
authors.forename: Bice
authors.initials: B
authors.lastname: Chini
authors.affiliation: †Laboratorio di Nanotecnologie, Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via G. Fantoli 16/15, 20138 Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ponti
mesh_terms: D001692:Biological Transport; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D004355:Drug Stability; D005019:Ethyl Ethers / Q000737:chemistry; D005290:Ferric Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000633:toxicity; D056945:Hep G2 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology*; D053758:Nanoparticles; D013451:Sulfonic Acids / Q000737:chemistry; D013499:Surface Properties
chemical_list: D005019:Ethyl Ethers; D005290:Ferric Compounds; D013451:Sulfonic Acids; C000499:ferric oxide