Development of novel treatment for tumor-bearing lymph node by lymphatic administration and sonoporation

Lymph node (LN) metastasis is thought to be an important factor to determine the treatment regimen or prognosis of patients. Chemotherapy of antitumor agents is one of the candidates for LN metastasis. However, systemic administration has shown poor efficacy in LN metastasis because only a small fraction of drugs can reach the target tissues. Here we show that local administration of antitumor agent, Doxorubicin (Dox), through lymphatic vessel (LV) with nano/micro bubbles (NMBs) and ultrasound (US) exposure enhances antitumor efficacy. We found that Dox and NMBs could reach the tumor-bearing LN through LV, and that US exposure to the LN enhanced the delivery of Dox into the tumor cells. Furthermore, we found that administration into the LV reduced the side effects compared to systemic administration. Our results demonstrate that lymphatic administration through LV and US exposure to the LN with tumor is a more valid treatment method than systemic administration.