Abstract
Chemotherapy for cancer plays a significant role in clinical situation. Systemic administration of anti-tumor agents causes drug dispersion in the whole body, however, this leads to poor efficacy in lymph node (LN) metastasis and severe side effects due to cytotoxicity to normal tissues. In this report, our aim is to develop a novel treatment method for LN metastasis. Our findings show that the lymphatic administration of drugs, doxorubicin, with a combination of nano/micro bubbles (NMBs) and ultrasound (US) enhances antitumor effect. When the solution of doxorubicin and NMBs were injected into the subiliac LN, they reached the tumor-bearing proper axillary LN (proper-ALN) through lymphatic vessels. Subsequently, the proper-ALN was also exposed to US. The NMBs with US exposure could increase cell membrane permeability transiently, resulting in the delivery of doxorubicin into the tumor cells in the LN efficiently. Furthermore, lymphatic administration inhibited acute toxicity compared to systemic administration. Our results demonstrate that the lymphatic administration of US with NMBs has a potential for the treatment of metastasis.
