Therapeutic effect of cisplatin given with a lymphatic drug delivery system on false-negative metastatic lymph nodes

Cancer Sci. 2017 Nov;108(11):2115-2121. doi: 10.1111/cas.13387. Epub 2017 Sep 15.

Abstract

Systemic administration of drugs into the blood circulation is standard treatment for prevention of metastasis. However, systemic delivery cannot maintain sufficiently high concentrations of anticancer drugs in lymph nodes (LN). Here, we show that giving cisplatin (CDDP) using a lymphatic drug delivery system (LDDS) has the potential to treat false-negative metastatic LN. We found that in MXH10/Mo-lpr/lpr mice, which develop systemic swelling of LN up to 10 mm in diameter, accumulation of indocyanine green (ICG), which has a similar molecular weight to CDDP, in a target LN was greater for lymphatic delivery of ICG than for systemic (i.v.) administration. Furthermore, CDDP administration with a LDDS inhibited tumor growth in false-negative metastatic LN and produced fewer adverse effects than systemically given CDDP. We anticipate that drug delivery using a LDDS will, in time, replace systemic chemotherapy for the treatment of false-negative metastatic LN.

Keywords: Cisplatin; MXH10/Mo-lpr/lpr mouse; lymph node metastasis; lymphatic drug delivery system; lymphatic network.

MeSH terms

  • Animals
  • Cisplatin / administration & dosage*
  • Cisplatin / adverse effects
  • Drug Delivery Systems*
  • Female
  • Humans
  • Indocyanine Green / chemistry
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Lymphatic Vessels / drug effects
  • Lymphatic Vessels / pathology
  • Mammary Neoplasms, Animal / drug therapy*
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / pathology
  • Mice

Substances

  • Indocyanine Green
  • Cisplatin