Impact of Tuning the Surface Charge Distribution on Colloidal Iron Oxide Nanoparticle Toxicity Investigated in Caenorhabditis elegans.

Loredana Amigoni,Chiara Pacini,Davide Prosperi,Lucia Salvioni,Maria Elena Regonesi,Barbara Sciandrone,Marco Giustra,Miriam Colombo,Paolo Tortora

doi:10.3390/nano11061551

Loredana Amigoni, Chiara Pacini + Show 7 more

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https://doi.org/10.3390/nano11061551

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Abstract

Assessing the toxic effect in living organisms remains a major issue for the development of safe nanomedicines and exposure of researchers involved in the synthesis, handling and manipulation of nanoparticles. In this study, we demonstrate that Caenorhabditis elegans could represent an in vivo model alternative to superior mammalians for the collection of several physiological functionality parameters associated to both short-term and long-term effects of colloidally stable nanoparticles even in absence of microbial feeding, usually reported to be necessary to ensure appropriate intake. Contextually, we investigated the impact of surface charge on toxicity of superparamagnetic iron oxide coated with a wrapping polymeric envelop that confers them optimal colloidal stability. By finely tuning the functional group composition of this shallow polymer–obtaining totally anionic, partially pegylated, partially anionic and partially cationic, respectively–we showed that the ideal surface charge organization to optimize safety of colloidal nanoparticles is the one containing both cationic and anionic groups. Our results are in accordance with previous evidence that zwitterionic nanoparticles allow long circulation, favorable distribution in the tumor area and optimal tumor penetration and thus support the hypothesis that zwitterionic iron oxide nanoparticles could be an excellent solution for diagnostic imaging and therapeutic applications in nanooncology.

Highlights

Superparamagnetic iron oxide nanoparticles (NPs) are one of the most intensively studied colloidal NPs in biology and medicine thanks to their unique magnetic properties that make them ideal tools for several applications, including bioseparation [1], biosensing [2], their use as targeted contrast agents for magnetic resonance imaging [3,4], drug delivery [5], gene therapy [6], regenerative medicine [7] and magnetic hyperthermia treatment of cancer [8,9]
We investigated the effect of treating C. elegans nematodes with 12-nm superparamagnetic iron oxide NPs coated with a common amphiphilic polymeric surfactant that allows obtaining excellent colloidal dispersion of the NPs in life-compatible aqueous solution
The cores were phase transferred by adding poly-maleic acid conjugated with Poly-Maleic Acid Conjugated with Dodecylamine (PMDA), an amphiphilic polymer, which is able to intercalate their hydrophobic tails in an oleic acid-covered nanosurface [35]

Summary

Introduction

Superparamagnetic iron oxide nanoparticles (NPs) are one of the most intensively studied colloidal NPs in biology and medicine thanks to their unique magnetic properties that make them ideal tools for several applications, including bioseparation [1], biosensing [2], their use as targeted contrast agents for magnetic resonance imaging [3,4], drug delivery [5], gene therapy [6], regenerative medicine [7] and magnetic hyperthermia treatment of cancer [8,9]. In order to obtain high-quality iron oxide NPs for biomedical applications, at least two important requirements are mandatory. This, in turn, is a major factor underlying their toxicity. To prevent these phenomena, the nature of NP coating is of paramount importance. The coating material is a key element in the functionalization of the NPs with targeting molecules and drugs [11]

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