Design of New Cancer Nanotherapeutics Which Controls Active Gaseous Molecules <i>in Vivo</i>

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  • 活性ガス分子を操るナノ粒子とがん化学療法
  • Symposium Review 活性ガス分子を操るナノ粒子とがん化学療法
  • Symposium Review カッセイ ガス ブンシ オ アヤツル ナノ リュウシ ト ガン カガク リョウホウ

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Abstract

　Reactive oxygen species (ROS) are known to play a variety of roles in many important events in vivo. However, the overproduction of ROS causes serious adverse effects to living beings. Numerous drugs have been developed and applied to reduce overproduced ROS, but these have failed to be clinically approved. Since most of these antioxidants are low molecular weight (LMW) compounds, they not only eliminate ROS related to diseases, but also destroy the essential redox reactions necessary for basic energy production in living bodies. In the mitochondria of normal cells, ATP production by electron transport chain is carried out, and a large amount of ROS is thus generated; however, LMW antioxidants also nonspecifically enter normal cells and affect essential oxidation. To improve selective antioxidant properties without damage to these normal redox reactions, we designed new polymer antioxidants. These polymers have self-assembling properties and form nanoparticles (RNPs) in which nitroxide radicals covalently attach as a side chain of the hydrophobic segment in the amphiphilic block copolymers, which are then compartmentalized into the solid core of the nanoparticles. Unlike LMW antioxidants, RNPs have extremely poor in vivo toxicity, as they are less likely to be taken up by healthy cells. Since one of RNPs, RNPN has pH-sensitive disintegration properties, it disintegrates at pH lower than 7.0 such as solid tumors and inflammation. It can therefore be used in pH responsive bioimaging and therapy. We have used RNPs experimentally in the treatment of several diseases and confirmed their effectiveness.<br>

Journal

  • YAKUGAKU ZASSHI

    YAKUGAKU ZASSHI 138 (7), 911-918, 2018-07-01

    The Pharmaceutical Society of Japan

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