Researchers at the University of California, Davis have developed a peptide-decorated DM-1 conjugated nanotherapeutic agent for targeted cancer therapy.
Microtubules and dynamic filamentous cytoskeletal proteins are important therapeutic targets in tumor cells. Mertansine (DM1) is a powerful tubulin polymerization inhibitor that prevents microtubule assembly while also killing various cancer cells at low nM concentration. DM1 is currently considered a standard treatment for malignancies including breast cancer, lung cancer, and melanoma however DM1 treatments have severe side effects including neurotoxicity, gastrointestinal toxicity, and fatigue because of a lack of tumor specificity. Existing treatments, such as trastuzumab conjugates (T-DM1) and general antibody drug conjugates (ADCs), are limited by low drug content, high clearance, and high manufacturing costs. There is a need to produce a DM1 conjugate that is more stable and enhances the tumor-targeting ability of DM1.
Researchers at the University of California, Davis have developed a DM1 hybrid telodendrimer with targeting agents decorating the surface of the nanomicelle, to enhance its tumor targeting ability. By using copper-free ‘Click’ chemistry to decorate the surface of the nanomicelle with potent ligands, the DM1 hybrid telodendrimer keeps the anticancer activity of DM1 without the risk of premature drug release. In multiple in vitro tests involving ovarian and lung cancer tumors, the DM1 hybrid showed better anti-tumor activity and less toxicity compared with free DM1 and non-targeted DM1-nano. Additionally, the DM1 hybrid showed improved drug solubility, blood circulation time, and cellular uptake efficiency.
DM1, mertansine, nanotherapeutic, lung cancer, breast cancer, melanoma, antibody drug conjugate, tumor, cancer, telodendrimer