Advances in the use of MT1-MMP-targeted nanobodies and peptides for therapeutic delivery in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) represents a particularly aggressive subtype of breast cancer characterized by the absence of estrogen and progesterone hormone receptors, as well as human epidermal growth factor receptor-2 (HER2) expression. This absence leads to a lack of approved targeted therapies, a poor prognosis, and restricted treatment options. Patients with TNBC primarily rely on cytotoxic chemotherapy; however, their tumors often exhibit rapid relapse and metastasis. Recent studies demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP) is significantly overexpressed in TNBC, promoting tumor invasion, metastasis, and resistance to conventional therapies by degrading the extracellular matrix (ECM). No clinically approved therapies targeting MT1-MMP exist, highlighting a significant knowledge gap in precision oncology for TNBC. This review examines the function of MT1-MMP in breast cancer. It poses a key question: Do novel nanobody- and peptide-based targeting strategies that focus on MT1-MMP enhance the specificity and efficacy of therapy and diagnosis for TNBC? This study systematically reviews preclinical advancements in the development of MT1-MMP-targeted nanobodies and peptides, detailing their mechanisms of action, in vivo efficacy, and translational obstacles. The focus is on preclinical findings, existing limitations, and future directions for enhancing the therapeutic and diagnostic potential of targeting MT1-MMP in TNBC. The findings indicate that targeting MT1-MMP with synthetic nanobodies and peptides may establish a basis for customized anti-metastatic therapies in TNBC. The ongoing refinement and enhancement of these strategies may improve therapeutic precision and decrease metastatic progression. © 2025 The Authors.