Abstract Lymph node metastasis is one of the major pathways for tumor formation and it is difficult to deliver chemotherapeutics at therapeutic concentrations to lymph node metastasis. This study prepared methyl poly(ethylene glycol)-distearoylphosphatidylethanolamine/doxorubicin (MPEG-DSPE/DOX) micelle for the treatment of lymph node metastasis. The MPEG-DSPE/DOX micelle prepared were of spherical morphology with a particle size of 20 ± 5 nm. The uptake rates of DOX and MPEG-DSPE/DOX micelle by A375 cells were 51.2% and 88.7%, respectively. The phagocytosis rate of MPEG-DSPE/Rhodamine B micelle by RAW264.7 cells was 17.2-fold lower than for Rhodamine B alone. After subcutaneous injection, MPEG-DSPE micelle underwent lymphatic absorption and accumulated in popliteal lymph nodes. MPEG-DSPE/DOX micelle significantly alleviated damage to the subcutaneous tissue of the injection sites compared with DOX alone. We established a model of nude mice bearing lymph node metastasis of A375 cells. After subcutaneous injection, the weights of both the popliteal and iliac lymph nodes of the MPEG-DSPE/DOX micelle group were significantly lower than in the saline and DOX groups. MPEG-DSPE/DOX micelle effectively killed the tumor cells in popliteal and iliac lymph nodes. In conclusion, MPEG-DSPE micelle is a promising drug delivery system for the treatment of lymph node metastasis.
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