Gold nanoparticles as innovative therapeutics for oral mucositis: A review of current evidence

Oral mucositis (OM) remains a debilitating side effect in patients undergoing cancer therapy. DNA damage and oxidative stress generated by radiation and/or chemotherapy activate key inflammatory pathways, ultimately resulting in the destruction of the epithelial barrier, leading to microbial colonization, and ulceration. These ulcerative lesions are often extremely painful, compromising nutrition and oral hygiene, requiring intravenous nutritional support, resulting in longer periods of hospitalization and increased cost. Ulcers often increase the risk of secondary infection, disrupting cancer therapy and patient prognosis. Despite these issues, there is no approved therapy to mitigate OM. Ultrasmall (< 10 nm) spherical gold nanoparticles (AuNPs) with low toxicity offer unique size- and surface chemistry-dependent anti-inflammatory and antioxidant properties. However, physicochemical design of AuNPs, including size, capping agent, and surface charge critically influence their colloidal stability, toxicity, and therapeutic efficacy. AuNP below 10 nm demonstrate increased therapeutic efficacy due to the high surface area-to-volume ratio, however, particles smaller than 2 nm also show increased potential for inducing cellular death. Furthermore, anionic capping agents make AuNPs less toxic with increased anti-inflammatory response, while cationic particles are potent antimicrobials but toxic. Thus, surface chemistry modulation is a promising strategy to design AuNPs (< 10 nm) as potential therapeutic agents for OM. This review provides a comprehensive overview of the OM pathophysiology, discusses current interventional concepts, critically analyses the existing literature on AuNP as an anti-inflammatory, antioxidant, and antimicrobial agent and highlights the benefits and challenges associated with using AuNPs as a therapeutic agent against OM.