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.

The ²²⁵Ac radioisotope exhibits very attractive nuclear properties for application in radionuclide therapy. Unfortunately, the major challenge for radioconjugates labelled with ²²⁵Ac is that traditional chelating moieties are unable to sequester the radioactive daughters in the bioconjugate which is critical to minimize toxicity to healthy, non-targeted tissues. In the present work, we propose to apply TiO₂ nanoparticles (NPs) as carrier for ²²⁵Ac and its decay products. The surface of TiO₂ nanoparticles with 25 nm diameter was modified with Substance P (5-11), a peptide fragment which targets NK1 receptors on the glioma cells, through the silan-PEG-NHS linker. Nanoparticles functionalized with Substance P (5-11) were synthesized with high yield in a two-step procedure, and the products were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and thermogravimetric analysis (TGA). The obtained results show that one TiO₂-bioconjugate nanoparticle contains in average 80 peptide molecules on its surface. The synthesized TiO₂-PEG-SP(5-11) conjugates were labelled with ²²⁵Ac by ion-exchange reaction on hydroxyl (OH) functional groups on the TiO₂ surface. The labelled bioconjugates almost quantitatively retain ²²⁵Ac in phosphate-buffered saline (PBS), physiological salt and cerebrospinal fluid (CSF) for up to 10 days. The leaching of ²²¹Fr, a first decay daughter of ²²⁵Ac, in an amount of 30% was observed only in CSF after 10 days. The synthesized ²²⁵Ac-TiO₂-PEG-SP(5-11) has shown high cytotoxic effect in vitro in T98G glioma cells; therefore, it is a promising new radioconjugate for targeted radionuclide therapy of brain tumours.

Recent advances in the field of nanotechnology application in nuclear medicine offer the promise of better therapeutic options. In recent years, increasing efforts have been made on developing nanoconstructs that can be used as carriers for immobilising alpha (α)-emitters in targeted drug delivery. In this publication, we provide a comprehensive overview of available information on functional nanomaterials for targeted alpha therapy. The first section describes why nanoconstructs are used for the synthesis of α-emitting radiopharmaceuticals. Next, we present the synthesis and summarise the recent studies demonstrating therapeutic applications of α-emitting labelled radiobioconjugates in targeted therapy. Finally, future prospects and the emerging possibility of therapeutic application of radiolabelled nanomaterials are discussed.