A novel copper-based nanosystem for augmented breast cancer photothermal and chemodynamic therapy

Sep 30, 2026

Metastasis and recurrence drive mortality in breast cancer, and current surgery and chemotherapy remain insufficient for metastatic disease. The study evaluates multifunctional copper-cysteine nanoparticles (Cu-Cys NPs) as a platform that integrates photothermal therapy (PTT) and chemodynamic therapy (CDT). DL- and L-Cu-Cys nanoparticles are assembled via Cu2+–cysteine coordination, followed by characterization of photothermal conversion and ROS generation. In vitro cytotoxicity and apoptosis in 4T1 cells are assessed with MTT and apoptosis assays, while in vivo tumor growth, metastasis, and systemic toxicity are examined in 4T1 tumor-bearing mice under intratumoral administration, showing effective tumor ablation and metastasis inhibition with low toxicity.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Photothermal therapy (PTT)

Chemodynamic therapy (CDT)

Rationale for copper-based PTT+CDT nanosystems

RSC Advances PAPER Cite this: RSC Adv., 2026, 16, 2167 Received 22nd October 2025 Accepted 18th December 2025 DOI: 10.1039/d5ra08100a[rsc.li/rsc-advances](rsc.li/rsc-advances) A novel copper-based nanosystem for augmented breast cancer photothermal and chemodynamic therapy Mohammad Seyedhamzeh,†a Farzaneh Falahi,†b Ali Kalantari-Hesari,c Kimia Esmaeilzadeh,a Laleh Salarilak,a Hadi Bagheri,a Shayesteh Bochani,a Satar Youseﬁasl,d Helia Behrouzfar,e Mohammad Esmaeil Akbari*fand Aziz Maleki *ag Among the most common cancers, metastasis and recurrence are the major causes of mortality in breast cancer. Current treatments, such as surgery and chemotherapy, have so far been inadequate in managing metastatic disease. This paper focuses on the potential of multi-functional copper-cysteine nanoparticles (Cu-Cys NPs) as a platform that incorporates PTT and CDT against this challenge. The DL-and L-Cu-Cys NPs were constructed through a straightforward coordination reaction between Cu2+ and cysteine ligands (DLand L), followed by detailed characterizations regarding their photothermal conversion eﬃciency and reactive oxygen species (ROS) generation capability. In vitro cytotoxicity and apoptosis of the 4T1 breast cancer cells treated with the prepared NPs were studied through MTT and apoptosis assays, respectively. Tumor growth, metastasis, and systemic toxicity in vivo were studied in intratumoral administrations in 4T1 tumor-bearing mice. The combined PTT and CDT not only remarkably ablated the primary tumor but also inhibited breast cancer metastasis with high eﬃciency. This work thus demonstrates the potential of combining PTT and CDT using a single nanosystem for treatment of metastatic tumors. 1. Introduction Breast cancer has globally been the leading diagnosed cancer in females.1 At present, surgery and chemotherapy are common methods to treat primary breast cancer.2 The main limitation of the methods is cancer metastasis and recurrence, contributing to the majority of cancer-related deaths worldwide.3 Photothermal therapy (PTT) has attracted tremendous attention in the past decades due to its non-invasiveness, high eﬃciency, and spatio-temporal selectivity. Using this approach near-infrared (NIR) light is absorbed by a photothermal agent, producing heat upon irradiation by the light, thus leading to aZanjan Pharmaceutical Nanotechnology Research Center (ZPNRC), Zanjan University of Medical Sciences, Zanjan 45139-56184, [Iran. E-mail: maleki@zums.ac.ir](Iran. E-mail: maleki@zums.ac.ir)bDepartment of Medical Biotechnology, School of Medicine, Zanjan University of Medical Science, Zanjan 45139-56111, Iran cDepartment of Basic Sciences, Faculty of Veterinary Medicine, Bu-Ali Sina University, Iran dDental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran eFaculty of Veterinary Medicine, Science and Research Branch of Islamic Azad University, Tehran, Iran fCancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran gDepartment of Pharmaceutical Nanotechnology, School of Pharmacy, Zanjan University of Medical Science, Zanjan 45139-56111, Iran † These authors contributed equally. elevated local tumor temperature and, ultimately causing irreversible tumor cell death. In addition, recent studies have also witnessed that PTT can boost immunological responses to eliminate the remaining cancer cells, thus preventing further metastasis.4–6 PTT may also be combined with other therapeutic approaches such as chemodynamic therapy, photodynamic therapy, gene therapy, and chemotherapy to realize improved therapeutic outcomes.7,8 Chemodynamic therapy (CDT) has emerged as a novel therapeutic modality utilizing Fenton or Fenton-like reactions to destroy cancer cells via conversion of endogenous H2O2 in the tumor microenvironment (TME) to highly cytotoxic hydroxyl radicals (cOH) .9,10 In 2023, an in situ activatble nitrobenzene-cysteine-

FAQs

What problem does the copper-cysteine nanosystem target in breast cancer?

It targets metastatic disease and recurrence, two major causes of breast-cancer mortality, by combining photothermal and chemodynamic mechanisms within one nanosystem.

How are the DL- and L-copper-cysteine nanoparticles prepared?

They are constructed through a coordination reaction between Cu2+ and cysteine ligands, followed by detailed physicochemical characterization.

How is therapeutic efficacy evaluated in vitro and in vivo?

In vitro, cytotoxicity and apoptosis of 4T1 breast cancer cells are measured using MTT and apoptosis assays. In vivo, tumor growth, metastasis, and systemic toxicity are assessed in 4T1 tumor-bearing mice after intratumoral administrations.

Sep 30, 2026

Uploaded by Alex Sinclair