Direct delivery of a cytotoxic anticancer agent into the metastatic lymph node using nano/microbubbles and ultrasound

• Published in: PloS one Vol. 10; no. 4; p. e0123619
• Main Authors: Sato, Takuma, Mori, Shiro, Sakamoto, Maya, Arai, Yoichi, Kodama, Tetsuya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.04.2015; Public Library of Science (PLoS)
• Subjects: Animal tissues; Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Antitumor activity; Apoptosis; Biomedical engineering; Breast cancer; Breast carcinoma; Cancer metastasis; Cancer therapies; Cell cycle; Cell Line, Tumor; Cell Survival; Chemotherapy; Cisplatin - administration & dosage; Contrast agents; Cytotoxicity; Drug delivery; Drug delivery systems; Drug dosages; Drug Screening Assays, Antitumor; Experiments; Female; Gene expression; Injections, Intralymphatic; Lymph; Lymph nodes; Lymph Nodes - diagnostic imaging; Lymphadenopathy; Lymphatic Metastasis; Lymphatic system; Metastases; Metastasis; Mice, Inbred C3H; Microbubbles; Neoplasm Transplantation; Penicillin; Therapy, Computer-Assisted; Ultrasonic imaging; Ultrasonography; Ultrasound; Urology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123619

Direct injection of an anticancer agent into a metastatic lymph node (LN) has not been used as a standard treatment because evidence concerning the efficacy of local administration of a drug into a metastatic LN has not been established. Here we show that the combination of intralymphatic drug delivery with nano/microbubbles (NMBs) and ultrasound has the potential to improve the chemotherapeutic effect. We delivered cis-diamminedichloroplatinum (II) (CDDP) into breast carcinoma cells in vitro and found that apoptotic processes were involved in the antitumor action. Next, we investigated the antitumor effect of intralymphatic chemotherapy with NMBs and ultrasound in an experimental model of LN metastasis using MXH10/Mo-lpr/lpr mice exhibiting lymphadenopathy. The combination of intralymphatic chemotherapy with NMBs and ultrasound has the potential to improve the delivery of CDDP into target LNs without damage to the surrounding normal tissues. The present study indicates that intralymphatic drug delivery with NMBs and ultrasound will potentially be of great benefit in the clinical setting.