Therapeutic Exosomes for Oral Cancer

Oral cancer (OC) is a common type of malignant tumor. OC cell-derived exosomes (OC-Exo) are involved in tumor growth, invasion, and metastasis. Due to their good biocompatibility and almost no immune rejection, exosomes can be used as carriers for drug delivery. Creative Biolabs has rich experience in exosome drug delivery and is confident to solve the research and development needs of OC-related exosome drugs.

Oral cancer (OC) and Exosome

OC is the sixth most common malignant tumor, which occurs in the oral cavity and oropharynx. The scope of OC includes lips, the base of tongue, tongue, gums, the floor of mouth, palate, tonsils, oropharynx, and the rest of the oral cavity. Oral squamous cell carcinoma is the most common pathological type in OC, accounting for about 90%. In recent years, the morbidity and mortality of OC have been increasing year by year worldwide. OC has a poor prognosis, with a 5-year survival rate of only about 50%. During the development of OC, OC cell-derived exosomes (OC-Exo) can transport their contents (DNA, RNA, protein, etc.) to target cells, which can affect chemotherapy resistance and sensitivity, angiogenesis, Immune response, proliferation, and migration of OC cells to promote or inhibit OC. For example, OC-Exo carries a highly expressed epidermal growth factor receptor (EGFR), which can enter epithelial cells and promote epithelial-to-mesenchymal transition (EMT), thereby promoting the metastasis of OC cells. However, OC-Exo can act on immune cells to activate immune responses and inhibit tumor progression. NAP1 in OC-Exo can inhibit OC by increasing the cytotoxicity of natural killer cells (NK cells) through the IRF-3 pathway.

Fig.1. Summary of exosomes as potential targets for oral cancer therapy. (Liu, 2022)

Engineered Exosomes and OC Therapy

Surgery combined with radiotherapy and chemotherapy is the main method of OC treatment at present, but the overall effect is not ideal. Nanoscale exosomes are biocompatible, stable, and targeted. With the deepening of exosome research, exosomes can be used as drug targets or drug carriers for the treatment of OC. Cisplatin resistance has been one of the obstacles in the treatment of OC. In 3D OC spheroids and xenograft mouse models, exosomes loaded with miR-155 inhibitors can restore FOXO3a expression and suppress EMT, downregulate drug efflux transporters and suppress stemness markers in cisplatin-resistant OCs expression, which ultimately increases the sensitivity of OC to cisplatin. This engineered exosome provides an adjunctive therapeutic strategy for cisplatin therapy in OC.

Fig.2. MiR-155 Inhibitor-Laden Exosomes Reverse Resistance to Cisplatin in a 3D Tumor Spheroid and Xenograft Model of Oral Cancer. (Sayyed, 2021)

In OC cells, COL10A1 was up-regulated, whereas miR-101-3p was down-regulated. miR-101-3p targets COL10A1. A research group found that human bone marrow mesenchymal stem cells (hBMSCs) overexpressing miR-101-3p could carry miR-101-3p into OC cells via exosomes. miR-101-3-loaded exosomes inhibited the proliferation, invasion, and migration of OC cells by inhibiting COL10A1. The therapeutic exosomes are still in the research stage and are expected to be applied in the treatment of OC.

Fig.3. Exosomes derived from microRNA-101-3p-overexpressing hBMSCs suppress OC cell proliferation, invasion, and migration. (Xie, 2019)

In addition, as one of the common oral potentially malignant diseases (OPMD), oral leukoplakia is easily converted to OC. miR-185 is known to be significantly reduced in the buccal tissue of OC patients. It has been found that engineered exosomes loaded with miR-185 induced cell apoptosis through the Akt/NF-κB/caspase-9 pathway, which significantly slowed the development of OPMD. Exo-miR-185 is expected to be used to prevent the conversion of OPMD to OC.

Fig.4. Delivery of mesenchymal stem cells-derived extracellular vesicles with enriched miR-185 inhibits progression of OPMD. (Wang, 2019)

For the past few years, Creative Biolabs has been providing best-in-class services through our excellent exosome development platform, designed to work with you to explore exosome medicines. If you are interested in our services, please contact us for more details.

References

Liu, H.; Huang, Y.; et al. Current Status, Opportunities, and Challenges of Exosomes in Oral Cancer Diagnosis and Treatment. International Journal of Nanomedicine. 2022, 17:2679-2705.
Sayyed, AA.; Gondaliya, P.; et al. MiR-155 Inhibitor-Laden Exosomes Reverse Resistance to Cisplatin in a 3D Tumor Spheroid and Xenograft Model of Oral Cancer. Molecular Pharmaceutics. 2021, 18(8):3010-3025.
Xie, C.; Du, LY.; et al. Exosomes derived from microRNA-101-3p-overexpressing human bone marrow mesenchymal stem cells suppress oral cancer cell proliferation, invasion, and migration. Molecular and Cellular Biochemistry. 2019, 458(1-2):11-26.
Wang, L, Yin, P.; et al. Delivery of mesenchymal stem cells-derived extracellular vesicles with enriched miR-185 inhibits progression of OPMD. Artificial Cells Nanomedicine and Biotechnology. 2019, 47(1):2481-2491.