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

Abstract

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

<p>Cinnamaldehyde and Doxorubicin Co-Loaded Graphene Oxide Wrapped Mesoporous Silica Nanoparticles for Enhanced MCF-7 Cell Apoptosis</p>

“…The ROS detection tests employed the DCFH-DA as the ROS marker to evaluate the ROS generation in MCF-7 cells induced by different CA or DOX preparations, which is hydrolyzed to DCF and generate highly green fluorescent signal once reacted with the intracellular ROS. 39 From Figure 10A and B , the intracellular ROS levels increased significantly after incubated by different CA preparations. The ROS levels of different experimental groups were 3.50 (MSN CA @GO DOX -HA), 3.26 (MSN CA @GO DOX ), 2.08 (MSN CA ), and 2.20 (CA) times of the blank control group, respectively.…”

Galangin Inhibits Gastric Cancer Growth Through Enhancing STAT3 Mediated ROS Production

“…Furthermore, STAT3 overexpression almost completely abolished the ROS accumulation induced by galangin treatment, indicating galangin induced ROS generation through STAT3 suppression. Many researches have proved that ROS enhanced cell apoptosis ( Cui et al, 2018 ; Dong et al, 2019 ), however, it has not been found that STAT3 also modulates ROS levels. Our results demonstrated that STAT3 activation inhibited ROS overload.…”

<p>Homoharringtonine Exerts an Antimyeloma Effect by Promoting Excess Parkin-Dependent Mitophagy</p>

“…High metabolic levels are a hallmark of tumor progression, including myeloma progression. 40 Excess mitophagy induced by HHT decreases the number and percentage of mitochondria, 41 which accelerates MM cell death due to the lack of energy metabolism (Figure 6). Taken together, HHT submit your manuscript | www.dovepress.com…”