Articles
Publication Date: 2026
Biomedicine and Pharmacotherapy (07533322)194
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.
Publication Date: 2026
Journal of Molecular Graphics and Modelling (10933263)142
Bioluminescence, the emission of light by living organisms, results from chemiluminescent reactions facilitated by enzymes like luciferases. Among these, NanoLuc (NLuc) stands out due to its exceptional brightness, stability, and compact structure, making it a valuable tool in bioassays and imaging applications. NLuc is a 19.1 kDa monomeric enzyme derived from the deep-sea shrimp Oplophorus gracilirostris. Its structure comprises eleven antiparallel β-strands forming a β-barrel, capped by four α-helices. To enhance its versatility, NLuc has been engineered into split forms. Despite the advancements in split NLuc applications, several impediments exist that can be addressed to improve these systems. Recently the spectacular allosteric mechanisms of NLuc has been reported. Based on that, the enzyme exhibits homotropic negative allostery, where product binding to an allosteric site inhibits substrate binding at the catalytic site. Ongoing research into its structural dynamics and allosteric behaviors continues to expand its potential applications, while efforts to enhance the efficiency of its split forms aim to broaden its utility in complex biological assays. In this in silico assay, we performed dynamic simulations for both the various forms of apo-NLuc and the docking complex with the substrate and product. As a result, we clarify the sources of malfunctions in split NLuc and explore various aspects of split NLuc technologies. We also examine some hypotheses of NLuc mechanisms that display the complex behavior of this luciferase. © 2025
