<p>Regulating intracellular ROS signal by a dual pH/reducing-responsive nanogels system promotes tumor cell apoptosis</p>

• DOI: 10.2147/ijn.s208089
• Publication Date: 2019-07-22T20:02:08Z
• Authors: Kai Dong; Qiuya Lei; Runhao Guo; Xianglong Wu; Yanni Zhang; Ning Cui; Jianyu Shi; Tingli Lu
• Keywords: 0301 basic medicine; Medicine (General); Intracellular Space; TPGS; Nanogels; Apoptosis; Polyethylene Glycols; Mice; 03 medical and health sciences; R5-920; International Journal of Nanomedicine; Animals; Humans; Polyethyleneimine; Vitamin E; Acrolein; Original Research; 0303 health sciences; Hydrogen-Ion Concentration; Mitochondria; Drug Liberation; Oxidative stress; Doxorubicin; MCF-7 Cells; Reactive oxygen species; Reactive Oxygen Species; Cinnamaldehyde

Purpose: The levels of reactive oxygen species (ROS) in tumor cells are much higher than that normal cells, and rise rapidly under the influence exogenous or endogenous inducing factors, eventually leading to apoptosis cells. Therefore, this study prepared a dual pH/reducing-responsive poly ( N -isopropylacrylamide-co-Cinnamaldehyde-co-D-α-tocopheryl polyethylene glycol 1000 succinate, P ss NCT) nanogels, which employed two ROS inducers, cinnamaldehyde (CA) D-α-tocopheryl succinate (TPGS), selectively induce by regulating Methods: NCT nanogels were free radical precipitation polymerization crosslink between pH-sensitive hydrazone reducing-sensitive disulfide bonds, followed physicochemical morphological characteristics investigations. Plasma stability, pH/reducing responsive degradation vitro release also assessed. In cell experiments, cytotoxicity different first detected. intracellular mitochondrial functions then evaluated. Moreover, western-blot assays verify association elevation Results: exhibited round-like hollow structure with diameter smaller 200nm. stable plasma, while showed rapid acidic reducing environments, thus achieving significant CA TPGS these media. Furthermore, sufficient amplification signals was induced synergistically function on mitochondria, resulted opening apoptotic pathway enhanced MCF-7 However, barely affected L929 owing their lower basal levels. Conclusion: specific regulation method achieved could be explored kill according difference kinds Keywords: species, oxidative stress, cinnamaldehyde, TPGS,