Immunomodulation of macrophages by methylglyoxal conjugated with chitosan nanoparticles against Sarcoma-180 tumor in mice

Methylglyoxal (MG), the potent anticancer agent has been conjugated to a nontoxic, biocompatible polymer, chitosan, to protect it from in vivo enzymatic degradation. This polymeric complex, 'Nano-MG' shows remarkable antitumor property and elicits macrophage-mediated immunity in tumor bearing mice on intravenous (0.4 mg/kg body wt/day) treatment more efficiently than MG (20 mg/kg body wt/day). These activated macrophages appear more in numbers in the peritoneum and produce more superoxide and nitrite. Moreover, immunomodulatory cytokines and surface receptors of these macrophages like iNOS, IFN-gamma, TNF-alpha, IL-1 beta, IL-6, M-CSF, TLR-4 and TLR-9 also exhibit marked up-regulation in Sarcoma-180 tumor bearing mice after Nano-MG treatment compared to untreated tumor bearing counterpart. Hence, Nano-MG acts as an immunostimulant in tumor bearing mice to combat cancer at conspicuously lower dose, probably due to its longer circulation time in blood. (C) 2013 Elsevier Inc. All rights reserved.