Hybrid Radiobioconjugated Superparamagnetic Iron Oxide-Based Nanoparticles for Multimodal Cancer Therapy.

Michał Żuk,Marcin Wolski,Agnieszka Majkowska-Pilip,Magdalena Osial,Aleksander Bilewicz,Paweł Krysiński,Weronika Gawęda

doi:10.3390/pharmaceutics13111843

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used for biomedical applications for their outstanding properties such as facile functionalization and doping with different metals, high surface-to-volume ratio, superparamagnetism, and biocompatibility. This study was designed to synthesize and investigate multifunctional nanoparticle conjugate to act as both a magnetic agent, anticancer immunological drug, and radiopharmaceutic for anticancer therapy. The carrier, 166Ho doped iron oxide, was coated with an Au layer, creating core-shell nanoparticles ([166Ho] Fe3O4@Au. These nanoparticles were subsequently modified with monoclonal antibody trastuzumab (Tmab) to target HER2+ receptors. We describe the radiobioconjugate preparation involving doping of a radioactive agent and attachment of the organic linker and drug to the SPIONs’ surface. The size of the SPIONs coated with an Au shell measured by transmission electron microscopy was about 15 nm. The bioconjugation of trastuzumab onto SPIONs was confirmed by thermogravimetric analysis, and the amount of two molecules per one nanoparticle was estimated with the use of radioiodinated [131I]Tmab. The synthesized bioconjugates showed that they are efficient heat mediators and also exhibit a cytotoxic effect toward SKOV-3 ovarian cancer cells expressing HER2 receptors. Prepared radiobioconjugates reveal the high potential for in vivo application of the proposed multimodal hybrid system, combined with magnetic hyperthermia and immunotherapy against cancer tissues.

Highlights

Feraheme® [15], Feridex I.V.® [16], and GastroMARK® [17], and much more [10]. Thanks to their heat generation capability under the alternating magnetic field (AMF) they can work as efficient therapeutic agents
The basis of hyperthermia relies on the fact that elevated temperatures localized within a tumor can damage and/or kill malignant cancer cells within the body
We present a facile synthesis of radioactive SPIONs doped with 166 Ho radioisotope and coated with a gold layer against holmium leaking from the structure of the magnetic core

Summary

Introduction

Superparamagnetic iron oxide nanoparticles (SPIONs) exhibit unique physicochemical properties [1,2,3], making them an attractive material for various biomedical applications including drug delivery [4,5,6], chemo-photothermal therapy [7,8], magnetic hyperthermia [9,10], magnetic resonance imaging (MRI) [11,12], and gene magnetofection [13,14].Due to their properties, iron oxide-based nanoparticles, known as ferumoxytol, have already gained approval for use as MRI contrast agents and as iron deficiency therapeutics by the Food and Drug Administration (FDA). Superparamagnetic iron oxide nanoparticles (SPIONs) exhibit unique physicochemical properties [1,2,3], making them an attractive material for various biomedical applications including drug delivery [4,5,6], chemo-photothermal therapy [7,8], magnetic hyperthermia [9,10], magnetic resonance imaging (MRI) [11,12], and gene magnetofection [13,14]. Numerous cell studies have shown that hyperthermia causes programmed cell death (apoptosis) as well

Methods

Results

Conclusion