Направленная доставка противотуберкулезных и фотосенсибилизирующих препаратов в опухоль-ассоциированные и M. tuberculosis-инфицированные макрофаги с использованием наноносителей

Туберкулёз остаётся одной из важнейших глобальных проблем общественного здравоохранения, входя в первую десятку основных причин, уносящих человеческие жизни и занимая первое место по смертности среди всех инфекционных заболеваний. При этом наиболее сложной проблемой туберкулеза, как и множества других инфекционных заболеваний, является лекарственная устойчивость возбудителя . Основным клеточным резервуаром M. tuberculosis (МБТ) являются макрофаги клетки врожденной иммунной системы, которые во взаимодействии с данным патогеном могут приобретать сложный фенотип с преимущественно антивоспалительными, иммуносупрессивными свойствами и формируют метаболически привилегированную среду, способствующую выживанию и внутриклеточной персистенции МБТ. В настоящем обзоре фенотип таких макрофагов обозначен как М2 (альтернативно активированные макрофаги). В обзоре систематизированы современные подходы к таргетной доставке противотуберкулезных препаратов в МБТ-инфицированные макрофаги с использованием высокомолекулярных и наноразмерных носителей. Рассмотрены стратегии пассивного и активного таргетирования, включая придание частицам векторных свойств лигандами к рецепторам М2-макрофагов, обсуждаются методы перепрограммирования функционального фенотипа макрофагов и использования наноразмерных биомиметиков; особое внимание уделяется направленной доставке в инфицированные клетки фотосенсибилизаторов для антимикробной фотодинамической терапии. Обобщенные данные свидетельствуют, что комбинированные нанотерапевтические подходы, сочетающие прямой антимикробный эффект с модуляцией локального иммунного ответа, открывают новые возможности для преодоления лекарственной устойчивости и эрадикации МБТ.

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