Ran, Wei; Liu, Xiaoyu; Chang, Lu; Cai, Ying; Zheng, Chao; Liu, Jia; Li, Yaping; Zhang, Pengcheng published the artcile< Self-assembling mertansine prodrug improves tolerability and efficacy of chemotherapy against metastatic triple-negative breast cancer>, Quality Control of 2127-03-9, the main research area is self assembling mertansine prodrug nanoparticle drug delivery system; Chemotherapy; Prodrug; Self-assembly; Supramolecular; Triple-negative breast cancer.
Metastatic triple-neg. breast cancer is one of the most devastating cancer types. Systemic chemotherapy is necessary, but its clin. performance is largely limited by severe side effects. Herein, we report a mertansine prodrug, which could self-assemble into spherical nanoparticles in water and readily convert into active mertansine at the presence of glutathione. The self-assembling mertansine prodrugs (SAMPDs) entered cancer cells via a caveolae-mediated pathway and exhibited potent cytotoxicity. The self-delivering SAMPDs did not cause hemolysis, and more importantly increased maximum tolerated dose (MTD) of mertansine by 8 folds via reducing free mertansine exposure in most of the major organs. SAMPDs improved intratumoral drug exposure and showed dose-dependent antitumor activity. When dosed at MTD, SAMPDs inhibited primary tumor growth and pulmonary metastasis by 80% and 95%, while mertansine dosed at MTD only reduced primary tumor growth and metastasis by <50% and 60%, resp. Our results reveal the mechanism of in vivo biotransformation of self-assembling prodrug and highlight the unique advantages of self-assembling prodrug strategy in improving the efficacy and safety of chemotherapy. Journal of Controlled Release published new progress about Antitumor agents. 2127-03-9 belongs to class pyridine-derivatives, and the molecular formula is C10H8N2S2, Quality Control of 2127-03-9.