• Using Copper-Cysteamine Nanoparticles for Enhanced Radiotherapy in Melanoma Treatment
  • Mohammadreza Nazarian,1,*
    1. Student Research Committee, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran.


  • Introduction: According to the World Health Organization report, skin cancer has been reported as the fifth most common cancer in the world. Skin cancer arises from unrepaired deoxyribonucleic acid (DNA) damage in skin cells, leading to genetic defects or mutations in the skin. Melanoma, basal cell carcinoma, and squamous cell carcinoma are three major types of skin cancer. Among them, melanoma is the most severe form and accounts for approximately 4% of all newly diagnosed cancers annually in the United States. Melanoma treatment is still a major challenge in the clinic. Treatments include radiation, chemotherapy, surgery, immune therapy, hormone therapy, and targeted therapy. Although these treatments are generally effective, they have some drawbacks. For example, radiotherapy is one of the most common and effective cancer treatments, however, it can have high side effects. Hence, it is crucial to improve radiation efficacy, reduce its dose, and develop a method to increase the dose to the tumor tissue while minimizing radiation to the surrounding tissue. Several techniques have been investigated to minimize the side effects of radiation therapy, including combining radiotherapy with photodynamic therapy, chemotherapy, and immunotherapy. One effective method to reduce the side effects and enhance the killing efficacy is to use radiosensitizers to assist the radiation treatment. Recently, various nanoparticle radiosensitizers, such as copper-cysteamine nanoparticles (Cu-Cy NPs), gold nanoparticles, silver nanoparticles, and hafnium oxide nanoparticles, have been studied as novel radiosensitizers. Cu-Cy NPs are unique compared to other nanoparticle radiosensitizers because Cu-Cy NPs act as photosensitizers and can be activated by various types of radiation, including X-rays, microwaves, and ultrasound, to produce reactive oxygen species (ROS). In this review, we investigated the use of Cu-Cy NPs for radiation improvement in melanoma cell lines
  • Methods: The Web of Science, Science Direct, PubMed, and Google Scholar databases were searched up to July 2024, utilizing various keyword combinations: melanoma, Copper-Cysteamine nanoparticle, radiotherapy, photodynamic therapy, and skin cancer.
  • Results: Studies have shown that when Cu-Cy NPs are placed in an acidic environment, they can release copper ions and accelerate the production of ROS in biological systems without light. Exposure of Cu-Cy NPs to X-rays has been shown to stimulate the production of singlet oxygen, hydroxyl radicals, and other ROS, which inhibits tumor growth. ROS can damage or kill tumor and vascular endothelial cells via apoptosis and necrosis pathways. The results showed that Cu-Cy-mediated PDT can stimulate strong anti-tumor immune responses by promoting the maturation of dendritic cells (DCs). This leads to the activation of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells, and inhibits the M2 macrophages in the tumor microenvironment (TME). As a result, tumor growth is halted by killing or suppressing tumor cells. Moreover, the size of nanoparticles plays a vital role in influencing their properties and performance. In the case of the 40 nm Cu–Cy NPs, their larger surface area compared to other NPs leads to the production of more ROS. Additionally, The cells absorb the 40 nm NPs more effectively. The 40nm Cu-Cy NPs efficiently prevented melanoma when exposed to X-rays. These findings confirmed that the combination of Cu-Cy NPs and X-rays promoted apoptosis and/or necrosis of melanoma cells.
  • Conclusion: Studies showed that Cu–Cy NP radiosensitizers can efficiently improve X-ray radiation to destroy melanoma cells by inducing generation ROS, apoptosis, and necrosis.
  • Keywords: melanoma, Copper-Cysteamine nanoparticles, radiotherapy, and photodynamic therapy