Sublingual delivery of nanoparticles to lymph nodes for head and neck cancer surgery and chemotherapy
Lymphatic metastasis is a predominant mechanism/route of cancer metastasis. In head and neck cancer, primary tumor cells migrate into the lymphatic vessels and grow inside of lymph nodes in the neck. Then, the tumor cells further spread to the distant sites of body through the blood stream or lymphatic system. In fact, more than 90% of metastases occur in sentinel lymph nodes. One of the reasons for failure in head and neck cancer therapy is due to distant metastases. Clinical cases with lymph node metastases have a poorer prognosis than those without nodal disease. Therefore, it is critical to identify and visualize the lymph nodes in the neck for diagnosis, cancer treatment, and surgery. Recently, real-time fluorescence imaging using indocyanine green (ICG) dye has been frequently used to identify lymph nodes during surgery. However, this method has not been fully optimized for oral cancers and detection/visualization of deep cervical lymph nodes.
In this study, we will address this limitation through sublingual delivery of nano-sized emulsions to improve the detection of lymph nodes for intrasurgical guidance. To achieve effective targeting and good retention of imaging agents in lymph nodes, we will design ICG-containing nano-sized emulsions (nanoemulsions) with 10- 50 nm in diameter. To target the sentinel lymph nodes in the neck, the nanoemulsions will be delivered through a sublingual route. The Specific Aims of this pilot study are to (1) synthesize ICG-containing nanoemulsions and (2) determine the in vivo efficiency of sublingual delivery of nanoemulsions to lymph vessels and their retention in lymph nodes. This study is significant because the expected results will contribute to the development of effective and simple fluorescence guidance during surgery, which will improve the outcomes of patients with head and neck cancer. While this study is focused on lymphatic imaging, this approach can be extended to lymph node-targeting delivery of cancer drugs.