Abstract
Suppression of axillary lymph node metastasis (ALNM) is an important goal in the treatment of breast cancer. While several therapies directed to ALNM have been evaluated, effective and safe treatments for ALNM in triple negative breast cancer (TNBC) have not been established yet, especially against initial/small metastases. Here, we demonstrated the therapeutic effect of an anthracycline drug, epirubicin (EPI)-loaded polymeric micelles equipped with pH-triggered drug release property (EPI/m) against ALNM of TNBC. EPI/m effectively inhibited the spread of the primary tumor and the growth of ALNM, through selective accumulation and penetration in both primary tumor and vascularized ALNM, as well as efficient drug activation triggered by the intratumoral acidic environment. Furthermore, we revealed that the improvement of the activated drug distribution of EPI/m contributed to dose-dependent enhancement of the antitumor effect through expansion of the therapeutic window. These findings highlight the utility of pH-responsive property in EPI/m for the treatment of ALNM in TNBC.
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