The role of nanotherapy in head and neck squamous cell carcinoma by targeting tumor microenvironment

Abstract

Head and neck squamous cell carcinomas (HNSCCs) refers to a group of highly malignant and pathogenically complex tumors. Traditional treatment methods include surgery, radiotherapy, and chemotherapy. However, with advancements in genetics, molecular medicine, and nanotherapy, more effective and safer treatments have been developed. Nanotherapy, in particular, has the potential to be an alternative therapeutic option for HNSCC patients, given its advantageous targeting capabilities, low toxicity and modifiability. Recent research has highlighted the important role of the tumor microenvironment (TME) in the development of HNSCC. The TME is composed of various cellular components, such as fibroblasts, vascular endothelial cells, and immune cells, as well as non-cellular agents such as cytokines, chemokines, growth factors, extracellular matrix (ECM), and extracellular vesicles (EVs). These components greatly influence the prognosis and therapeutic efficacy of HNSCC, making the TME a potential target for treatment using nanotherapy. By regulating angiogenesis, immune response, tumor metastasis and other factors, nanotherapy can potentially alleviate HNSCC symptoms. This review aims to summarize and discuss the application of nanotherapy that targets HNSCC's TME. We highlight the therapeutic value of nanotherapy for HNSCC patients.

Keywords: head and neck squamous cell carcinoma; immune microenvironment; immune response; nanotherapy; tumor microenvironment.

Figure 1

The tumor microenvironment of HNSCC contains various cellular components, including tumor cells, immune related cells, stromal cells and some non-cellular components, such as cytokines, chemokines, EVs, ECM and the hypoxia environment.

Figure 2

The available approaches of nanotherapy for HNSCC. A variety of nanoparticles, including liposome, metal particle, polymeric nanoparticle, micelle and magenic particles, are used for the treatment of HNSCC by carrying protein/peptide, antibodies, drugs, molecules and siRNA. These nanoparticles may function by enhancing the radiotherapy, combining photothermal therapy, inducing immune therapy, and accurately delivering agents to TME.

Figure 3

Illustration of nanotherapy targeting TME in HNSCC. Nanoparticles were injected intravascular or intratumor and subsequently induced the anti-angiogenesis (with quinacrine, PTX, VEGF siRNA, VEGF transcriptional repressor, GD16 peptide and resveratrol as the core agents), immune response (with imiquimod, dasatinib and oxaliplatin, aPD-1, and IL-1α and cetuximad as the critical agents), and the remodeling of hypoxia and ECM (with cisplatin and metformin, HIF-1α siRNA and DOX and ICG) in the TME.