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Cells do not crave zwitterionic nanoparticles

Significance Statement

Magnetic nanoparticles have recently aroused much interest since they can be harnessed to detect and monitor diseases and to treat them.  A major hurdle to successful medical application of magnetic nanoparticles is our mononuclear phagocyte system (MPS). The  phagocytic cells of the MPS are very efficient clearing cellular debris and extraneous micoorganisms from our body. Unfortunately, MPS is also good at clearing nanoparticles, especially when they adsorb proteins from the blood, thus preventing them to do the job they were intended for. Therefore, magnetic nanoparticles with good colloidal stability in biological fluids, lack of protein adsorption, and undergoing minimal aspecific cell internalization are required for successful medical application. We synthesized magnetic iron oxide nanoparticles and coated them with a layer of very short zwitterionic dopamine sulfonate (ZDS) molecules. Each zwitterionic dopamine sulfonate molecule comprises an anchor group grafting to the iron oxide surface and a pair of plus and minus charges located at the nanoparticle outer surface. The nanoparticles are globally neutral but have a very polar surface.

We have shown that these zwitterionic nanoparticles have good colloidal stability and do not adsorb proteins, and that HepG2 cells internalize them in tiny amount. Therefore, the three main requirements we described above are met. Furthermore, internalized zwitterionic nanoparticles are sent to the lysosomes where are dissolved. Thus, zwitterionic dopamine sulfonate magnetic nanoparticles are a promising building block to create nanoparticles that are able to reach their diagnostic or therapeutic target before they are cleared by the MPS and that do not accumulate in our body.

Figure legend: TEM image of zwitterionic iron oxide nanoparticles (diameter: 9 nm) along with a pictorial sketch of a nanoparticle and the chemical structure of zwitterionic dopamine sulfonate. Inset: HepG2 cells after 6 h treatment with zwitterionic nanoparticles (green: nanoparticles, blue: nucleus, red: lysosomes).

Cells do not crave zwitterionic nanoparticles- Global Medical Discovery
















Journal Reference

Zwitterion-Coated Iron Oxide Nanoparticles: Surface Chemistry and Intracellular Uptake by Hepatocarcinoma(HepG2) Cells.

Langmuir. 2015 Jul 7;31(26):7381-90.

Mondini S1, Leonzino M2, Drago C1, Ferretti AM1, Usseglio S1, Maggioni D3, Tornese P2, Chini B2, Ponti A1.

Show Affiliations
  1. Laboratorio di Nanotecnologie, Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, via G. Fantoli 16/15, 20138 Milano, Italy.
  2. Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche, via L. Vanvitelli 32, 20133 Milano, Italy.
  3. Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milano, Italy.


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.

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