“…Inspired by the results of Trastuzumab-ANCs toward HER2-expressing cancer cells, we tested the applicability of ANCs to target cells with different overexpressed receptors. Specifically, tumor-specific mucin 1 (tMuc1) and epidermal growth factor receptor (EGFR) show great potential in different breast cancer subtypes. , In contrast to tumor tissue, where the tMuc1 epitope is exposed, the Muc1 epitope in healthy tissue is highly glycosylated masking the epitope. , The unique glycosylation status and common appearance in breast cancers (>90%) of mucin 1 proteins are quite appealing for the development of ADCs that specifically target tMuc1. ,, In this work, we conjugated an anti-tMuc1 antibody, TAB004, to the nanogels to target tMuc1-positive breast cancer cells. The choice of cargo was established from an IC50 screening of four commonly used drugs, including DOX, PTX, DM1, and SN38, where SN38 showed the highest sensitivity to both tMuc1 and EGFR-expressing cell lines (Figure S17).…”