Department of Chemical and Biomolecular Engineering, Yonsei University, Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Department of Pharmacy, Korea University, Sejong-ro, Jochiwon-eup, Sejong, 30019, Republic of Korea.
Small. 2017 Aug;13(32). doi: 10.1002/smll.201700818. Epub 2017 Jul 10.
Reactive oxygen species (ROS) produced during mitochondrial oxidative phosphorylation play an important role as signal messengers in the immune system and also regulate signal transduction. ROS production, initiated as a consequence of microbial invasion, if generated at high levels, induces activation of the MEK (mitogen-activated protein kinase kinase)/ERK (extracellular signal-regulated kinase) pathway to promote cell survival and proliferation. However, viruses hijack the host cells' pathways, causing biphasic activation of the MEK/ERK cascade. Thus, regulation of ROS leads to concomitant inhibition of virus replication. In the present study, poly(aniline-co-pyrrole) polymerized nanoregulators (PASomes) to regulate intracellular ROS levels are synthesized, exploiting their oxidizing-reducing characteristics. Poly(aniline-co-pyrrole) embedded within an amphiphilic methoxy polyethylene glycol-block-polyphenylalanine copolymer (mPEG-b-pPhe) are used. It is demonstrated that the PASomes are water soluble, biocompatible, and could control ROS levels successfully in vitro, inhibiting viral replication and cell death. Furthermore, the effects of homopolymerized nanoregulators (polypyrrole assembled with mPEG-b-pPhe or polyaniline assembled with mPEG-b-pPhe) are compared with those of the PASomes. Consequently, it is confirmed that the PASomes can regulate intracellular ROS levels successfully and suppress viral infection, thereby increasing the cell survival rate.
活性氧（ROS）在线粒体氧化磷酸化过程中产生，作为免疫系统中的信号信使发挥着重要作用，同时也调节信号转导。ROS 的产生是微生物入侵的结果，如果产生的水平较高，则会启动丝裂原活化蛋白激酶激酶（MEK）/细胞外信号调节激酶（ERK）途径的激活，从而促进细胞存活和增殖。然而，病毒会劫持宿主细胞的途径，导致 MEK/ERK 级联的双相激活。因此，ROS 的调节导致同时抑制病毒复制。在本研究中，合成了聚（苯胺-co-吡咯）聚合纳米调节剂（PASomes）以调节细胞内 ROS 水平，利用其氧化还原特性。将聚（苯胺-co-吡咯）嵌入两亲性甲氧基聚乙二醇嵌段-聚苯丙氨酸共聚物（mPEG-b-pPhe）中。结果表明，PASomes 水溶性好、生物相容性好，能够成功地在体外控制 ROS 水平，抑制病毒复制和细胞死亡。此外，还比较了均聚物纳米调节剂（mPEG-b-pPhe 组装的聚吡咯或 mPEG-b-pPhe 组装的聚苯胺）与 PASomes 的效果。因此，证实了 PASomes 可以成功地调节细胞内 ROS 水平，抑制病毒感染，从而提高细胞存活率。
