Revolutionizing radiotherapy: gold nanoparticles with polyphenol coating as novel enhancers in breast cancer cells—an in vitro study

Discover Nano Research Revolutionizing radiotherapy: gold nanoparticles with polyphenol coating as novel enhancers in breast cancer cells—an in vitro study Simona Tarantino1 · Annalisa Bianco1 · Mariafrancesca Cascione1,2 · Alessandra Carlà3 · Lia Fiamà3 · Riccardo Di Corato2,4 · Livia Giotta5 · Paolo Pellegrino2 · Anna Paola Caricato1 · Rosaria Rinaldi1,2 · Valeria De Matteis1,2 Received: 2 September 2024 / Accepted: 8 January 2025 © The Author(s) 2025  OPEN Abstract Breast cancer is the most common cancer among women, with over 1 million new cases and around 400,000 deaths annually worldwide. This makes it a significant and costly global health challenge. Standard treatments like chemotherapy and radiotherapy, often used after mastectomy, show varying effectiveness based on the cancer subtype. Combining these treatments can improve outcomes, though radiotherapy faces limitations such as radiation resistance and low selectivity for malignant cells. Nanotechnologies, especially metallic nanoparticles (NPs), hold promise for enhancing radiotherapy. Gold nanoparticles (AuNPs) are particularly notable due to their high atomic number, which enhances radiation damage through the photoelectric effect. Studies shown that AuNPs can act as effective radiosensitizers, improving tumor damage during radiotherapy increasing the local radiation dose delivered. Traditional AuNPs synthesis methods involve harmful chemicals and extreme conditions, posing health risks. Green synthesis methods using plant extracts offer a safer and more environmentally friendly alternative. This study investigates the synthesis of AuNPs using Laurus nobilis leaf extract and their potential as radiosensitizers in breast carcinoma cell lines (MCF-7). These cells were exposed to varying doses of X-ray irradiation, and the study assessed cell viability, morphological changes and DNA damage. The results showed that green-synthesized AuNPs significantly enhanced the therapeutic effects of radiotherapy at lower radiation doses, indicating their potential as a valuable addition to breast cancer treatment. 1 Introduction Breast cancer is the most prevalent cancer among women, with over 1 million new cases and approximately 400.000 deaths reported globally each year, according to the World Health Organization [1]. Consequently, this illness is one of the most significant and expensive health challenges worldwide. Chemotherapy and radiotherapy (RT) can be employed either before or after mastectomy for cancer treatment [2]. Specifically, neoadjuvant chemotherapy is often used in patients with locally advanced breast cancer to reduce tumor size before surgery, allowing for more conservative surgical options and improving operability [3]. Similarly, neoadjuvant radiotherapy, although less commonly used, may be * Valeria De Matteis, | 1Department of Mathematics and Physics “Ennio De Giorgi”, University of Salento, Via Arnesano, 73100 Lecce, LE, Italy. 2Institute for Microelectronics and Microsystems (IMM), CNR, Via Monteroni, 73100 Lecce, Italy. 3Oncological Center, “Vito Fazzi” Hospital of Lecce, Piazza Filippo Muratore 1, 73100 Lecce, Italy. 4Center for Biomolecular Nanotechnologies, Istituto Italiano Di Tecnologia (IIT), 73010 Arnesano, Italy. 5Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, Via per Monteroni, 73100 Lecce, Italy. Discover Nano (2025) 20:10 | https://doi.org/10.1186/s11671-025-04186-x Vol.:(0123456789) Research Discover Nano (2025) 20:10 | https://doi.org/10.1186/s11671-025-04186-x considered in specific cases to enhance local control, particularly in cases where the tumor is fixed to the chest wall or there are concerns about achieving negative surgical margins [4]. The effectiveness of X-ray therapy varies depending on the breast cancer subtype. Combining these treatments can significantly enhance therapeutic outcomes [5]. Therefore, radiotherapy for breast cancer can reduce its efficiency and affect normal tissues for several reasons. Among these the radiation resistance induces the loss of susceptibility to damage from the treatment and the low selectivity to malignant cells. In the pursuit of new strategies to enhance the effectiveness of radiotherapy at tumor sites, nanotechnologies offer promising potential due to their unique properties. [6–8]. Nanomaterials, especially metallic nanoparticles (NPs), are emerging as pivotal tools in revolutionizing the treatment of severe diseases, including cancer [9]. In particular, gold nanoparticles (AuNPs) have garnered and continue to receive considerable attention due to their physicochemical properties. Au has a high atomic number (Z = 79), that significantly amplify targeted radiation damage in both in vitro and in vivo settings. This enhancement is believed to occur through the photoelectric effect, which results in the emission of short-range Auger electrons and characteristic X-rays. These properties make AuNPs particularly suitable for radiotherapy (RT). [10, 11]. Indeed, AuNPs acting as effective radiosensitizers against cancer cells when exposed to RT significantly enhancing tumor damage in the localized site [12]. Additionally, the action of cancer-incubated and irradiated metallic NPs triggers biological mechanisms such as the suppression of thioredoxin reductase activity [13]. This is significant because numerous tumor cells express elevated levels of Thioredoxin (Trx) and thioredoxin reductase (TrxR), which may contribute to drug resistance during tumorigenesis. Therefore, inhibiting the Trx system could play a role in enhancing cancer therapy and improving the efficacy of chemotherapeutic agents [14], and equally important the radio sensitizing activity of metal NPs [15]. In literature, different kinds of AuNPs were used in combination with radiotherapy. Different works demonstrated the effectiveness of this kind of nanomaterial. Wu et al. [16] conjugated (RGD)4 peptides on polyethylene glycolylated (PEGylated) 15 nm AuNPs (P-AuNPs) (RGD/PAuNPs), and tested them on three breast cancer cell lines such as MDA-MB-231, Hs578T and SK-BR-3. After irradiating at 130 kV with doses up to 4 Gy, they found that RGD/P-AuNPs enhanced radiation effects by inhibiting the invasive activity of breast cancer cells. Teraoka et al. [17] conducted an in vitro study on the impact of AuNPs in RT, using the HSC-3 cell line derived from human head and neck carcinoma. Cancer cells were exposed to 5 nm AuNPs at four concentrations of 0.1 nM, 0.4 nM, 1.0 nM and 10 nM. The cell count was reduced to 50%, with the most significant effects at 4 Gy and 8 Gy radiation levels. Rahman et al. [18] performed experiments on bovine aortic endothelial cells to simulate endothelial tissue and assessed cell survival as a measure of dose enhancement. They observed dose enhancement factors, based on 90% cell survival, ranging from 4 to 25 at concentrations between 0.25 mM and 1 mM when cells were exposed to an 80 kVp (...truncated)