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

Nanomaterials

卷:9

Agnieszka Majkowska-Pilip¹  Aleksander Bilewicz¹  Marek Pruszyński¹  Łucja Dziawer¹  Damian Gaweł²  Marlena Godlewska²  Jerzy Jastrzębski³  Bogdan Wąs⁴ 

[1] Centre of Radiochemistry and Nuclear Chemistry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland;

[2] Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, Marymoncka 99/103, 01-813 Warsaw, Poland;

[3] Heavy Ion Laboratory, University of Warsaw, Pasteura 5A, 02-093 Warsaw, Poland;

[4] Institute of Nuclear Physics, Polish Academy of Sciences, Radzikowskiego 152, 31-342 Cracow, Poland;

关键词: α-nanobrachytherapy;    monoclonal antibody;    SKOV-3 ovarian cell line;    HER2 receptor;    α-emitter ²¹¹At;   

DOI  :  10.3390/nano9040632

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown