Multifunctional Nanoparticles Based on Iron Oxide and Gold-198 Designed for Magnetic Hyperthermia and Radionuclide Therapy as a Potential Tool for Combined HER2-Positive Cancer Treatment

Abstract

Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (Fe3O4) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody—trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy.

Doxorubicin- and Trastuzumab-Modified Gold Nanoparticles as Potential Multimodal Agents for Targeted Therapy of HER2+ Cancers

“…A very low signal was detected inside the cells (panel E/2), which may suggest the passive transport of particles. The obtained results were consistent with our previously reported studies with the AuNPs–Tmab bioconjugate [ 19 , 20 , 21 , 24 ] as well as data published by other groups [ 22 ].…”

Superparamagnetic Iron Oxide Nanoparticles (SPION): From Fundamentals to State-of-the-Art Innovative Applications for Cancer Therapy

“…Nevertheless, they demonstrated the use of 131 I-APTES functionalized SPION without magnetic-induced hyperthermia was sufficient to induce a significant lowering of the tumor growth rate [ 208 ]. Similarly, Zuk et al explored the potential of SPION containing a radioactive isotope of gold and functionalized with trastuzumab in order to target HER-2 positive cancer cells [ 209 ]. This strategy allowed the authors to induce a significant regression of spheroid growth.…”

Multimodal Radiobioconjugates of Magnetic Nanoparticles Labeled with ⁴⁴Sc and ⁴⁷Sc for Theranostic Application

“…Cytotoxicity studies with 47 Sc were performed with MTS assay according to the previously reported protocol [5]. LNCaP (10 x 10 3 ) and PC-3 (7.5 x 10 3 ) cells were seeded into 96-well plates 48 h before treatment and incubated in 37°C with 5% CO2-supplemented atmosphere.…”

“…In another publication 223 Ra-doped BaFe nanoparticles were presented as candidates for multimodal drug combining localized magnetic hyperthermia with internal α-therapy [4]. Magnetic nanoparticles labeled also with βemitters ( 188 Re, 198 Au, 90 Y, and 131 I) and Auger electrons emitters ( 111 In, 125 I) were also investigated, some of them in preclinical studies [5][6][7][8][9].…”

“…In medical applications, MNPs can be coated with a biocompatible polymer to increase stability and bioavailability [11] or coated with antibody for biomarker immobilization [12]. Among others, MNPs modified with Hyperbranched Polyglycerol (HPG) have attracted much attention for years [1][2][3][4][5][6][7][8][9][10][11][13][14][15]. Having three-dimensional structures and numerous internal and external functional groups, these compounds can serve as remarkable hosts for metal complexes, enzymes, and biomaterials.…”