Trastuzumab-Modified Gold Nanoparticles Labeled with 211 At as a Prospective Tool for Local Treatment of HER2-Positive Breast Cancer

• Published in: Nanomaterials (Basel, Switzerland) Vol. 9; no. 4
• Main Authors: Dziawer, Łucja, Majkowska-Pilip, Agnieszka, Gaweł, Damian, Godlewska, Marlena, Pruszyński, Marek, Jastrzębski, Jerzy, Wąs, Bogdan, Bilewicz, Aleksander
• Format: Journal Article
• Language: English
• Published: Switzerland 18-04-2019
• Subjects: monoclonal antibody; α-emitter 211At; HER2 receptor; SKOV-3 ovarian cell line; α-nanobrachytherapy
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano9040632

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 (
At), 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
At obtained by α irradiation of the bismuth target. The labeling yield of
At was greater than 99%.
At bioconjugates were stable in human serum. Additionally,
biological studies indicated that
At-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
At-AuNP-PEG-trastuzumab was effectively internalized and deposited near the nucleus. These findings show promising potential for the
At-AuNP-PEG-trastuzumab radiobioconjugate as a perspective therapeutic agent in the treatment of unresectable solid cancers expressing HER2 receptors.