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

• Published in: Cellular immunology 2014-01, Vol.287 (1), p.27-35
• Main Authors: Chakrabarti, Adrita, Talukdar, Dipa, Pal, Aparajita, Ray, Manju
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Chitosan - administration & dosage; Chitosan - chemistry; Cytokines - metabolism; Cytotoxicity, Immunologic - drug effects; Female; Gene Expression Regulation, Neoplastic - drug effects; Immunomodulation; Macrophage; Macrophages - drug effects; Macrophages - immunology; Mice; Nano-MG; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neoplasm Transplantation; Nitrites - metabolism; Pyruvaldehyde - administration & dosage; Pyruvaldehyde - chemistry; Reactive nitrogen species (RNS); Reactive oxygen species (ROS); Sarcoma - immunology; Sarcoma - therapy; Superoxides - metabolism; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-Like Receptor 9 - genetics; Toll-Like Receptor 9 - metabolism; Tumor
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2013.11.006

•We developed a methylglyoxal chitosan conjugate called ‘Nano-MG’.•This compound has anticancer and immunomodulatory role.•Nano-MG reduced murine Sarcoma-180 tumor volume.•Nano-MG upregulated macrophage cytokines in tumor bearing 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 (0.4mg/kg bodywt/day) treatment more efficiently than MG (20mg/kg bodywt/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-γ, TNF-α, IL-1β, 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.