Abstract
Simple SummaryThough radiation therapy remains a primary modality for head and neck cancer (HNC) management, the collateral damage to normal surrounding tissues and tumor relapse represent major challenges. Hence, it is imperative to develop safer and more effective HNC therapies. Metal and metal oxide nanoparticle-based radiosensitizers have been explored for their potential to overcome these challenges. The key impetus of this review was to shed light on ongoing metal and metal oxide nanoparticle-based radiosensitizers’ development and to address their success in in vitro and in vivo HNC models and in clinical translation.Although radiation therapy (RT) is one of the mainstays of head and neck cancer (HNC) treatment, innovative approaches are needed to further improve treatment outcomes. A significant challenge has been to design delivery strategies that focus high doses of radiation on the tumor tissue while minimizing damage to surrounding structures. In the last decade, there has been increasing interest in harnessing high atomic number materials (Z-elements) as nanoparticle radiosensitizers that can also be specifically directed to the tumor bed. Metallic nanoparticles typically display chemical inertness in cellular and subcellular systems but serve as significant radioenhancers for synergistic tumor cell killing in the presence of ionizing radiation. In this review, we discuss the current research and therapeutic efficacy of metal nanoparticle (MNP)-based radiosensitizers, specifically in the treatment of HNC with an emphasis on gold- (AuNPs), gadolinium- (AGdIX), and silver- (Ag) based nanoparticles together with the metallic oxide-based hafnium (Hf), zinc (ZnO) and iron (SPION) nanoparticles. Both in vitro and in vivo systems for different ionizing radiations including photons and protons were reviewed. Finally, the current status of preclinical and clinical studies using MNP-enhanced radiation therapy is discussed.
Highlights
Head and neck cancer (HNC) is the sixth most common cancer worldwide, with an estimated incidence of 53,260 cases and 10,750 deaths in 2020 alone [1]
Radiosensitization or dose augmentation produced by the addition of high Z atom metal nanoparticle (MNP) in target tumor tissues with photon radiation has been widely examined and recognized in the literature, while the use of MNPs with proton beam radiation continues to be an active area of research [45,46]
Though the underlying mechanisms for these differences were not obvious, this study clearly demonstrated that AuNPs augment the effect of radiation on a radioresistant mouse HNC and that radiation dose, energy, and HT together affect their efficacy, suggesting the possibility of using AuNPs as radiosensitizers for improved HNC
Summary
Head and neck cancer (HNC) is the sixth most common cancer worldwide, with an estimated incidence of 53,260 cases and 10,750 deaths in 2020 alone [1]. Additional strategies must be developed that maximize tumor control while minimizing surrounding tissue damage This is imperative in HNC because the primary tumor is often situated adjacent to radiosensitive organs with critical functions such as the salivary glands, thyroid, larynx, and swallowing apparatus [12]. Secondary electrons further augment radiation dose locally within the tumor and mediate ROS generation either by charge transfer to produce O2− from dissolved oxygen molecules or by energy transfer from fluorescent X-rays or bremsstrahlung X-rays The probability of this interaction depends on the incident radiation energy and the atomic Z value of the particle’s atoms [31,32]. 488-nm laser channel with increased ROS production after radiation treatment (Cesium-137 source) in the presence of a gold nanoparticle upon 4-Gy irradiation. (Unpublished data, Takiar laboratory, University of Cincinnati)
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