Continuously manufactured single-core iron oxide nanoparticles for cancer theranostics as valuable contribution in translational research.

Regina Bleul,Frank Wiekhorst,Christian Freese,Olaf Kosch,Hendrik Paysen,Abdulkader Baki

doi:10.1039/d0na00343c

Abstract

Micromixer technology was used to manufacture magnetic single core iron oxide nanoparticles that combine imaging as well as therapeutic functions. In a continuous, scalable and highly controllable manner, synthesis with biocompatible educts via an aqueous synthesis route was performed. Size control by varying relevant process parameters e.g. temperature was confirmed by transmission electron microscopy measurements of experimental series demonstrating the exceptional size control and homogeneity. Furthermore, analytical centrifugation evidenced the stably dispersed state of the single core nanoparticles in aqueous media. Size controlled production of single-core iron oxide nanoparticles was used to design optimized nanoparticles with a core diameter of about 30 nm, showing high signal amplitudes in Magnetic Particle Imaging (MPI) as a promising MPI tracer material. Moreover, therapeutic potential of these particles in magnetic fluid hyperthermia was evaluated and specific absorption rates (SAR values) up to 1 kW per g(Fe) were obtained, which exceed the comparable SAR value of Resovist® by more than a factor of three. Relaxometry measurements clearly confirmed the capacity of these single-core magnetic nanoparticles to generate significant T2-weighted magnetic resonance imaging (MRI) contrast that potentially allows multimodal imaging for monitoring the particles in vivo in a theranostic application scenario. Finally, first cell viability and apoptosis tests on endothelial cells did not show any cytotoxicity certifying a good biocompatibility of the iron oxide nanoparticles. This microtechnological approach provides reproducible, scalable single core iron oxide nanoparticles as highly performing tracers for MPI diagnosis as well as efficient heat generators for hyperthermia therapy. These preliminary results contribute to translational research in image guided cancer therapy – a further step from basic research to future medicine.

Highlights

Cancer is still one of the leading causes of death worldwide, responsible for an estimated one million deaths in 2018
Micro uidic systems for nanoparticle synthesis gained popularity in the last decade because of their promising potential in controlling critical stages such as nucleation and growth leading to improved size control, enhanced reproducibility and higher throughput than in batch synthesis.[26]
It is evident from the results presented so far that the properties of the single-core iron oxide magnetic nanoparticles synthesized by micromixer ow chemistry via an aqueous synthesis route can be tuned effectively by adjusting solely the temperature, the one relevant process parameter

Summary

Introduction

Cancer is still one of the leading causes of death worldwide, responsible for an estimated one million deaths in 2018. Preliminary studies on the continuous synthesis of iron oxide nanoparticles demonstrated the high potential of micromixer technology as a valuable tool for the development of new magnetic nanomaterials.[25] the performances of reported tracers for magnetic particle imaging at this time were still far below the performance of Resovist®, which is an MRI contrast agent and is presently considered as a gold standard for MPI.

Results

Conclusion