Green, scalable, low cost and reproducible flow synthesis of biocompatible PEG-functionalized iron oxide nanoparticles

Julien Mahin,Michael D Mantle,Luise Fanslau,Christoph O Franck,Laura Torrente-Murciano,Ljiljana Fruk,Hirak K Patra

doi:10.1039/d1re00239b

Abstract

A continuous synthesis strategy enabling the large-scale and cost-effective synthesis and functionalization of iron oxide nanoparticles in a single setup is developed, leading to fully biocompatible and application-ready PEG coated nanoparticles.

Highlights

We demonstrate the continuous, green, scalable and reproducible synthesis of highly stable PEGfunctionalized iron nanoparticles using a modular flow system
This stabilizer was designed with a nitrodopamine (NDA) moiety which possess high affinity to iron oxide acting as a strong anchoring group
A custom stabilizing heterobifunctional PEGbased molecule was designed with a nitrodopamine anchor on one side for strong binding to iron oxide and a carboxylic acid moiety on the other side to enable further derivatization by simple amide conjugation

Summary

Introduction

Iron oxide nanoparticles (Fe3O4NP) are widely investigated for biomedical applications, such as MRI contrast agents,[1,2,3,4] drug delivery,[5,6,7] magnetic hyperthermia cancer treatment,[8,9,10] theranostics,[11,12] cryopreservation,[13,14] etc. iron oxide is suited for biomedical applications because of its magnetic properties and low toxicity compared to other ferromagnetic materials such as cobalt and nickel.[15]. Iron oxide nanoparticles (Fe3O4NP) are widely investigated for biomedical applications, such as MRI contrast agents,[1,2,3,4] drug delivery,[5,6,7] magnetic hyperthermia cancer treatment,[8,9,10] theranostics,[11,12] cryopreservation,[13,14] etc. Designing a heterobifunctional nitrodopamine–PEG–COOH stabilizing agent results in free carboxylic acid moieties which can be used to further couple the iron oxide nanoparticles with any molecule of interest such as fluorophores or antibodies for bio-imaging and targeted drug delivery. This unique flexibility was illustrated here by functionalization of the nanoparticles with fluorescein. A full cost analysis was carried out, demonstrating the commercial viability of the synthetic process opening the door to the deployment of iron oxide nanoparticles in a wide range of biomedical applications

Synthetic strategy and reaction setup

Further derivatization

Cost analysis

Conclusions

Experimental section