nano-diamino-tetrac

Nano-diamino-tetrac (NDAT, also known as Nanotetrac) is a nanoparticulate formulation of diamino-tetrac (DAT), which itself is a derivative of tetraiodothyroacetic acid (tetrac). NDAT consists of DAT molecules conjugated to poly(lactic-co-glycolic acid) (PLGA) nanoparticles via stable amide bonds. The nanoparticle formulation was specifically designed to restrict the action of DAT to integrin αvβ3 receptors on the cell surface and prevent cellular uptake and nuclear access, thereby avoiding potential thyromimetic (genomic) effects that can occur with free tetrac or DAT. NDAT acts primarily by binding to the thyroid hormone receptor on the plasma membrane integrin αvβ3, a proneoplastic integrin highly expressed in cancer cells and rapidly dividing endothelial cells. Through this receptor interaction, NDAT competitively inhibits the binding of L-thyroxine (T4) and initiates anticancer signal transduction pathways. The mechanism involves inhibition of cancer cell proliferation, anti-angiogenesis, suppression of metastasis, promotion of apoptosis, and inhibition of immune checkpoint mechanisms. NDAT has demonstrated superior potency compared to unmodified tetrac in preclinical studies, with effects on gene expression including upregulation of tumor suppressor genes (p53, p21, CASP2, THBS1) and downregulation of pro-proliferative genes (CCND1, c-Myc, VEGF-A). The nanoparticle formulation also provides longer plasma circulation time and enhanced tumor bioavailability through the enhanced permeability and retention (EPR) effect. NDAT has shown efficacy in colorectal cancer cells regardless of K-RAS mutation status and has demonstrated the ability to reverse cetuximab resistance in K-RAS-mutant colorectal cancer.

Other names

DAT-conjugated PLGA nanoparticles