Our findings suggest the potential benefit of OximUNO as a TAM-depleting agent for TNBC treatment. Treatment with OximUNO reduced the progression of primary tumor lesions and pulmonary metastases, significantly diminished the number of CD206 + TAMs and increased the CD8/FOXP3 expression ratio (indicating immunomodulation). OximUNO exhibited no acute liver or kidney toxicity in vivo.

In the TNBC model, a fluorescently labeled mUNO-decorated St-PGA homed to CD206 + TAMs within primary lesions and metastases. OximUNO comprises a star-shaped polyglutamate (St-PGA) decorated with the CD206-targeting peptide mUNO that carries the chemotherapeutic drug doxorubicin (DOX). Here, we developed a novel TAM-depleting agent (“OximUNO”) that specifically targets CD206 + TAMs and demonstrated efficacy in a triple-negative breast cancer (TNBC) mouse model. Although many studies have explored the depletion of tumor-associated macrophages (TAM) as a therapeutic strategy for solid tumors, currently available compounds suffer from poor efficacy and dose-limiting side effects.

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