Enhancing radiotherapy for melanoma: the promise of high-Z metal nanoparticles in radiosensitization
Creators: name: Bemidinezhad, Abolfazl
name: Radmehr, Shaghayegh
name: Moosaei, Negin
name: Efati, Zohreh
name: Kesharwani, Prashant
name: Sahebkar, Amirhossein
Publisher: name: Taylor & Francis
Year: 2024
Subjects: Space Science
Medicine
Cell Biology
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified
Biological Sciences not elsewhere classified
Developmental Biology
Cancer

description: Melanoma is a type of skin cancer that can be challenging to treat, especially in advanced stages. Radiotherapy is one of the main treatment modalities for melanoma, but its efficacy can be limited due to the radioresistance of melanoma cells. Recently, there has been growing interest in using high-Z metal nanoparticles (NPs) to enhance the effectiveness of radiotherapy for melanoma. This review provides an overview of the current state of radiotherapy for melanoma and discusses the physical and biological mechanisms of radiosensitization through high-Z metal NPs. Additionally, it summarizes the latest research on using high-Z metal NPs to sensitize melanoma cells to radiation, both <i>in vitro</i> and <i>in vivo</i>. By examining the available evidence, this review aims to shed light on the potential of high-Z metal NPs in improving radiotherapy outcomes for patients with melanoma. Melanoma, a lethal skin cancer from melanocytes, causes 75% of skin cancer-related deaths worldwide. Rising incidence necessitates urgent interventions. Traditional treatments like surgery, chemotherapy, immunotherapy and radiotherapy (RT) have limitations. Nanomedicine, using nanoparticles (NPs) sized 1–100 nm, shows promise in enhancing cancer treatment, especially high-Z metal NPs (e.g., gold, platinum, gadolinium) in improving RT outcomes for melanoma. RT is vital for melanoma management, especially when surgery is not viable or cancer has spread. Combining RT with immune checkpoint inhibitors (ICI) improves outcomes in brain metastases. Fractionated RT enhances T cell responses, similar to vaccines. Studies suggest higher radiation doses may be more effective, with clinical studies indicating a median total dose of 30 Gy and BED &gt;39.0 Gy10. High-Z metal NPs can enhance RT by targeting cancer cells precisely while sparing healthy tissue. High-Z metal NPs like gold, magnetic iron oxide, gadolinium, copper-cysteamine and platinum enhance RT efficacy while preserving healthy tissue. Gold NPs enhance RT through unique properties like surface plasmon resonance. mIONs offer RT combined with hyperthermia, enhancing therapeutic outcomes. Gadolinium enhances MRI and RT, with AGuIX<sup>®</sup> NPs allowing precise imaging and targeted therapy. Other high-Z metals like copper-cysteamine and platinum enhance ROS production, improving treatment outcomes. Key design factors include material, size, shape, surface coating and charge. NP size affects biodistribution and clearance, with optimal sizes for tumor uptake being 20–60 nm. NP concentration and surface charge impact RT enhancement and cytocompatibility. Synthesis methods, including chemical, physical and green, ensure biocompatibility and reduced toxicity. Coatings improve stability and targeting, essential for passive and active strategies, enhancing treatment efficacy. Radiosensitization involves physical, chemical and biological phases. High-Z metal NPs enhance RT through the photoelectric effect and sary electron production, increasing local radiation doses. They modulate chemical reactions, enhancing DNA damage and ROS production. Biologically, NPs disrupt cell cycles, delay DNA repair and induce oxidative stress, increasing tumor cell radiosensitivity. High-Z metal nanoparticles show significant promise in enhancing radiotherapy for melanoma. Benefits include efficient x-ray absorption, targeted delivery and induction of oxidative stress. Key challenges like ensuring biocompatibility, understanding mechanisms and optimizing NP design need addressing before clinical translation. Continued research is essential for developing effective and safe NP-based therapies. Future prospects include using NPs for targeted radiation doses to melanoma cells, optimizing delivery strategies and conducting preclinical and clinical studies to validate efficacy and safety. Continued innovations in nanomedicine could lead to more targeted, effective and personalized cancer treatments, transforming oncology.