Extracellular Vesicle-Based Drug Delivery Systems for Head and Neck Squamous Cell Carcinoma: A Systematic Review

Abstract

It is estimated that there are over 890,000 new cases of head and neck squamous cell carcinoma (HNSCC) worldwide each year, accounting for approximately 5% of all cancer cases. Current treatment options for HNSCC often cause significant side effects and functional impairments, thus there is a challenge to discover more acceptable treatment technologies. Extracellular vesicles (EVs) can be utilized for HNSCC treatment in several ways, for example, for drug delivery, immune modulation, as biomarkers for diagnostics, gene therapy, or tumor microenvironment modulation. This systematic review summarizes new knowledge regarding these options. Articles published up to 11 December 2022, were identified by searching the electronic databases PubMed/MEDLINE, Scopus, Web of Science, and Cochrane. Only full-text original research papers written in English were considered eligible for analysis. The quality of studies was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool for Human and Animal Studies, modified for the needs of this review. Of 436 identified records, 18 were eligible and included. It is important to note that the use of EVs as a treatment for HNSCC is still in the early stages of research, so we summarized information on challenges such as EV isolation, purification, and standardization of EV-based therapies in HNSCC.

Keywords: drug delivery systems; exosomes; extracellular vesicles; head and neck squamous cell carcinoma; nanoparticles.

Figure 1

Flow diagram of the systematic literature search.

Figure 2

Overview of cancer antigens, immunosuppressive and anti-tumour immune cells in HNSCC. ALDH—aldehyde dehydrogenase, CAF—cancer-associated fibroblast, CEA—carcinoembryonic antigen, DC—dendritic cell, EBV—Epstein-Barr virus, EGFR—epithelial growth factor receptor, HERV—human endogenous retroviruses, HNSCC—head and neck squamous cell carcinoma, HPV—human papillomavirus, hTERT—human telomerase reverse transcriptase, IDO—indoleamine-2,3-dioxygenase, M1—macrophage 1, MAGE—melanoma-associated antigen, MDSC—myeloid-derived suppressor cell, MUCI—mucin-1, NK—natural killer cell, NY-ESO-I—New York esophageal squamous cell carcinoma-1, SSX—synovial sarcoma X, T reg—T regulatory cell.

Figure 3

Role of EVs in the tumour microenvironment and impact on the immune system in HNSCC; DC—dendritic cell, MDSC—myeloid-derived suppressor cell, NK—natural killer cell, T reg—T regulatory cell, TME—tumor microenvironment.