Block Copolymer Carrier Systems for Translymphatic Chemotherapy of Lymph Node Metastases

Abstract

The presence of lymph node metastases relevantly and significantly impairs disease-specific survival in patients suffering from squamous cell carcinoma of the upper aerodigestive tract. In a VX2 animal tumor model, we present an interstitial translymphatic therapeutic approach using cis-diaminedichloro-platinum(II) (CDDP) conjugated to a poly(ethylene oxide)-block-poly(lysine) (PEO-b-PLys) block copolymer tracking systems for the successful treatment of lymph node metastases. Most effective was the application of a high cargo-load CDDP tracking system (48 wt.% CDDP) curing 90% of the animals and causing only minor local side-effects. Systems containing 1 or 10 wt.% of CDDP were less effective but still cured 50% of the animals. Moreover, the administration of 1 or 10 wt.% of CDDP consistently limited tumor growth to the draining lymph nodes (50%) and prevented systemic distribution of the metastasis even with 1 wt.% CDDP load. The systems contained 0.25-0.003 mg/kg per body weight CDDP compared to 1 ml/kg per body weight as usually used for intravenous administration. This approach encourages further and more detailed research of a CDDP-based interstitial translymphatic administration of chemotherapy for lymphogenic metastasizing carcinomas in different body regions.