Mannosylated chitosan nanoparticle-based cytokine gene therapy suppressed cancer growth in BALB/c mice bearing CT-26 carcinoma cells.
Cancer immunotherapy relies on the ability of the immune system to destroy tumor cells selectively and to elicit a long-lasting memory of such activity. Interleukin-12 (IL-12) is an immunomodulatory cytokine produced primarily by antigen-presenting cells, which play an important role in promoting Th1-type immune response and cell-mediated immunity. To augment the antitumor immune action by in vivo IL-12 gene delivery, mannosylated chitosan (MC) was prepared to induce mannose receptor-mediated endocytosis of IL-12 gene directly into dendritic cells which reside within the tumor. Upon characterization, MC was proven to be suitable for IL-12 gene delivery due to good physicochemical properties and low cytotoxicity. In addition, MC exhibited much enhanced IL-12 gene transfer efficiency to dendritic cells rather than chitosan itself in terms of the induction of murine IL-12 p70 and murine IFN-gamma. In animal studies, intratumoral injection of MC/plasmid encoding murine IL-12 complex into BALB/c mice bearing CT-26 carcinoma cells clearly suppressed tumor growth and angiogenesis, and significantly induced cell cycle arrest and apoptosis. Therefore, this study provides a new MC-mediated cytokine gene delivery system for cancer immunotherapy.
Kim
Tae Hee
TH
Laboratory of Biomedical Polymer and Tissue Engineering, School of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Korea. chocs@plaza.snu.ac.kr.
Jin
Hua
H
Kim
Hyun Woo
HW
Cho
Myung-Haing
MH
Cho
Chong Su
CS
D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle; D048271:Chitosan / Q000737:chemistry*; D003713:Dendritic Cells / Q000637:transplantation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D007167:Immunotherapy / Q000379:methods; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008358:Mannose / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000188:drug therapy
D018664:Interleukin-12; D048271:Chitosan; D008358:Mannose