title: Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of doxorubicin, suppressing its adverse effect.
abstract: The ultimate goal of cancer chemotherapy is to achieve a cure without causing any adverse effects. We have developed a pH-sensitive redox nanoparticle (RNP(N)), which disintegrates under acidic conditions and exposes nitroxide radicals, leading to strongly scavenging reactive oxygen species (ROS). After intravenous administration of RNP(N) to tumor bearing mice, it effectively accumulated in tumors due to the leaky neovascular and immature lymphatic system and scavenged ROS, resulting in suppression of inflammation and activation of NF-кB, after disintegration of RNP(N) in the tumors. Pre-administration of RNP(N) prior to treatments with anticancer agents, doxorubicin, to tumor-bearing mice significantly suppressed the progression of tumor size, compared to low-molecular weight 4-hydroxy-TEMPO. Interestingly, the administration of RNP(N) suppressed adverse effects of doxorubicin to normal organs due to the scavenging ROS and suppression of inflammation, which was confirmed by reduction in lactate dehydrogenase and creatine phosphokinase activities in plasma. RNP(N) is thus anticipated as a novel and ideal adjuvant for cancer chemotherapy.
authors: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors: Toru
authors: T
authors: Yoshitomi
authors: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors: Yuki
authors: Y
authors: Ozaki
authors: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors: Sindhu
authors: S
authors: Thangavel
authors: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Master's School of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan; Satellite Laboratory, International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science (NIMS), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan. Electronic address: yukio@nagalabo.jp.
authors: Yukio
authors: Y
authors: Nagasaki
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009589:Nitrogen Oxides / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D016166:Free Radical Scavengers; D016328:NF-kappa B; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D004317:Doxorubicin; C039900:nitroxyl
keywords: Cancer chemotherapy; Doxorubicin; Nitroxide radical; Reactive oxygen species; Transcriptional factor; pH-responsive polymeric micelle