Highly localized
radiotherapy with
radionuclides is a commonly used treatment modality for patients with unresectable solid
tumors. Herein, we propose a novel α-nanobrachytherapy approach for selective
therapy of
human epidermal growth factor receptor 2 (HER2)-positive
breast cancer. This uses local intratumoral injection of 5-nm-diameter
gold nanoparticles (AuNPs) labeled with an α-emitter (211At), modified with
polyethylene glycol (PEG) chains and attached to HER2-specific
monoclonal antibody (
trastuzumab). The size, shape, morphology, and zeta potential of the 5 nm synthesized AuNPs were characterized by TEM (Transmission Electron Microscopy) and DLS (Dynamic Light Scattering) techniques. The
gold nanoparticle surface was modified by PEG and subsequently used for antibody immobilization. Utilizing the high affinity of
gold for heavy
halogens, the bioconjugate was labelled with 211At obtained by α irradiation of the
bismuth target. The labeling yield of 211At was greater than 99%. 211At bioconjugates were stable in human serum. Additionally, in vitro biological studies indicated that 211At-AuNP-PEG-trastuzumab exhibited higher affinity and cytotoxicity towards the HER2-overexpressing human ovarian SKOV-3 cell line than unmodified nanoparticles. Confocal and dark field microscopy studies revealed that 211At-AuNP-PEG-trastuzumab was effectively internalized and deposited near the nucleus. These findings show promising potential for the 211At-AuNP-PEG-trastuzumab radiobioconjugate as a perspective therapeutic agent in the treatment of unresectable solid
cancers expressing HER2 receptors.