| 초록 |
Nitric oxide (NO) is a free radical endogenously synthesized in the body and plays multiple physiological roles, including vasodilation, angiogenesis, neurotransmission, and immune response. Depending on its concentration and localization, NO changes its roles. We have hypothesized that site-specific accumulation of NO molecules controls tumor progression. Due to the poor bioavailability of NO, however, great efforts have been made to develop a methodology for the controlled delivery of exogenous NO in living systems. Most of trials were based on slow release of NO molecules from particle formulations. Due to the rapid diffusion, however, it is not easy to control releasing of NO from the particles. In this study, we have designed a new approach of macrophage-triggered cancer NO-immunotherapy. Inducible NO synthase (iNOS) in activated macrophages produces NO using arginine as a substrate. Since huge number of activated macrophage is infiltrated in tumor microenvironment, NO generation can be anticipated if L-arginine is delivered to tumor site. In this study, PEG-block-poly(L-arginine) was originally designed by new synthetic methodology.1 Our idea was to cooperate our PIC nanoparticle composed of PEG-b-PArg coupled with polyanion, and macrophage in tumor site to generate effective amount of NO molecules. After internalization of this nanoparticle into macrophages, significant increase in NO level was observed in vitro experiment. This nanoparticle can be delivered into tumor tissue via systemic administra-tion (EPR eff.) and confirmed to increase the anti-tumor activity.2 We believe that the PIC nanoparticle composed of poly(L-arginine) opens new strategy for cancer immunotherapy. (1) S. Kudo and Y. Nagasaki, Macromol. Rapid Commun., 36, 1916(2015). (2) S. Kudo and Y. Nagasaki, J. Control. Release, 217, 256(2015). |
