Физико-химические аспекты и биологическая активность конъюгатов нанодисперсного диоксида церия с сывороточным альбумином человека

Нанодисперсный диоксид церия (СеО₂) обладает уникальной каталитической активностью в реакциях с участием активных форм кислорода (АФК), играющих роль медиаторов ключевых сигнальных путей. Альбумин является наиболее распространенным белком плазмы крови, взаимодействие с которым может влиять как на свойства наночастиц СеО₂, так и на саму биомолекулу. На модели эмбриональных фибробластов легкого человека (in vitro) исследовано, как конъюгация нанодисперсного СеО₂ с альбумином влияет на ряд биохимических параметров: жизнеспособность клеток, уровень внутриклеточных АФК, экспрессию NOX4, NRF2 и NF-κB, окислительное повреждение и репарацию ДНК, апоптоз, пролиферацию клеток и аутофагию. Результаты демонстрируют, что связывание диоксида церия с альбумином изменяет его физико-химические свойства, способствуя более эффективному поглощению наночастиц СеО₂ клетками. Конъюгация СеО₂ с белком ослабляет влияние наночастиц на внутриклеточный баланс АФК и митохондриальный мембранный потенциал. Примечательно, что конъюгаты СеО₂ с альбумином индуцируют более сильную активацию NOX4, что приводит к повышенному генотоксическому стрессу. Однако этот эффект компенсировался более эффективной активацией систем репарации ДНК по сравнению с немодифицированным диоксидом церия. Помимо этого, конъюгаты наночастиц СеО₂ с белком модулировали сигнальные пути, усиливая подавление провоспалительного каскада NF-κB и активируя процессы аутофагии. Таким образом, конъюгация наночастиц СеО₂ с альбумином не только снижает их цитотоксичность, но и усиливает противовоспалительный и регенеративный потенциалы диоксида церия.

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