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

PLoS One. 2015 Apr 21;10(4):e0123619. doi: 10.1371/journal.pone.0123619. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Apoptosis
  • Cell Line, Tumor
  • Cell Survival
  • Cisplatin / administration & dosage*
  • Drug Screening Assays, Antitumor
  • Female
  • Injections, Intralymphatic
  • Lymph Nodes / diagnostic imaging
  • Lymphatic Metastasis
  • Mice, Inbred C3H
  • Microbubbles
  • Neoplasm Transplantation
  • Therapy, Computer-Assisted
  • Ultrasonography

Substances

  • Antineoplastic Agents
  • Cisplatin

Grants and funding

This study was supported in part by JSPS KAKENHI grant numbers 26293425 (SM), 26670856 (SM), 25293382 (MS), 24659834 (MS), 26242051 (TK) and 24650286 (TK). The funders did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.