The Combination of Intralymphatic Chemotherapy with Ultrasound and Nano-/Microbubbles Is Efficient in the Treatment of Experimental Tumors in Mouse Lymph Nodes

Intravenous chemotherapy is a therapeutic option for the treatment of lymph node metastasis, but the drugs often have difficulty accessing the lymphatic system. The aim of this study was to determine whether the combination of intralymphatic chemotherapy with ultrasound and nano-/microbubbles is active against tumors in mouse lymph nodes. Intralymphatic chemotherapy in mice with lymph nodes containing tumors was found to have a marked anti-tumor effect, compared with intravenous administration, and the addition of ultrasound combined with nano-/microbubbles enhanced the effect of the anti-cancer drug, but only when the drug was administered intralymphatically. Furthermore, decreases in the volumes and blood vessel densities of tumor-bearing lymph nodes are reliable measures of therapeutic effect, confirmed by histopathological evaluation. The main conclusion is that combining ultrasound with nano-/microbubbles and intralymphatic chemotherapy improves drug delivery to the lymphatic system and has a more potent anti-tumor effect.