Acidic pH value and oxidative stress caused by excess production of reactive oxygen species (ROS) are two of the most typical inflammatory markers. Each of them has received extensive interest as a target stimulus in inflammation. Curcumin (CUR), a member of ginger family, has been used as an antioxidant in the treatment of chronic inflammatory diseases. In this study, we developed self-assembled, pH-responsive N-palmitoyl chitosan nanoparticles with a Cy3 moiety (Cy3-NPCS NPs) to encapsulate a ROS-sensitive thioketal polymer (PPADT) and curcumin, and delivered them to lipopolysaccharide (LPS)-stimulated macrophages to mitigate regional inflammation. The PPADT-CUR-Cy3-NPCS (PCCN) NPs with sensitivity to both pH and ROS showed great inhibitory effects on ROS production, such as hydrogen peroxide (H2O2) and nitric oxide (NO‧). Based on the Förster Resonance Energy Transfer (FRET) effect, we further intracellularly monitored the drug releasing process, and hence better understood the correlation between the FRET effect and CUR release. From our result, the immune-responsive PCCN NPs are potent for both probing and curing of ROS-related diseases.

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