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

Abstract

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

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