Redox nanoparticle therapeutics to cancer--increase in therapeutic effect of doxorubicin, suppressing its adverse effect.
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.
['Yoshitomi|Toru|T|', 'Ozaki|Yuki|Y|', 'Thangavel|Sindhu|S|', 'Nagasaki|Yukio|Y|']
D000818:Animals D000903:Antibiotics, Antineoplastic D003692:Delayed-Action Preparations D004317:Doxorubicin D004357:Drug Synergism D016166:Free Radical Scavengers D006801:Humans D007249:Inflammation D051379:Mice D008807:Mice, Inbred BALB C D016328:NF-kappa B D053758:Nanoparticles D009369:Neoplasms D009589:Nitrogen Oxides D010084:Oxidation-Reduction D017382:Reactive Oxygen Species
Doxorubicin Cancer chemotherapy Nitroxide radical Reactive oxygen species Transcriptional factor pH-responsive polymeric micelle