Enhancing radiotherapy for melanoma: the promise of high-Z metal nanoparticles in radiosensitization

Abstract

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 in vitro and in vivo. 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.

Keywords: gold nanoparticle; high-Z material; melanoma; radiosensitization; radiotherapy.

Graphical abstract

Figure 1.

Passive, active and combination targeting at the tumor microenvironment. Passive targeting uses stealth-coated NPs, which induce a repulsive effect in opsonins. This effect stops opsonins from attaching to and marking the NPs' surface, preventing their removal from the organism. Tumor tissue has an undeveloped lymphatic system and defective blood vessel walls, causing the enhanced EPR effects. This causes NPs to accumulate in tumor tissue. Specific compounds conjugated onto NPs have a particular affinity for cancerous tissues in active targeting. The main goal is to avoid passive uptake via the EPR effect. Opsonins bind to NPs' surfaces in the circulatory system, allowing macrophages to recognize and remove them. Combining targeting techniques requires stealth coating and targeting ligand optimization to maximize circulation time. Combination coatings repel opsonins, preventing them from binding to and marking NPs. Biocompatibility, stability, passive tumor targeting and therapeutic cargo delivery to the tumor location are improved by this coating.

Figure 2.

Mechanisms of high-Z NPs radiosensitization. High-Z NPs interact with IR at the physical, chemical and biological phases, enhancing radiation effects. Two interactions cause photoelectric and Compton effects in the physical phase. The photoelectric effect occurs when a bound electron disappears from the photon, emission characteristic radiation. Photons and free electrons interact in the Compton effect, causing scattering at an angle θ. Consequently, NPs induce cellular damage through the increasing production of photoelectrons. During the chemical phase, ROS were generated due to the interaction between NPs and radiolysis water molecules. ROS induce apoptosis, while extremely low energy electrons chemically sensitize DNA to IR damage. Finally, NPs increase IR through oxidative stress, DNA damage, G2/M cell cycle arrest and DNA repair inhibition during the biological phase.