Cinnamaldehyde-Based Poly(ester-thioacetal) To Generate Reactive Oxygen Species for Fabricating Reactive Oxygen Species-Responsive Nanoparticles

Due to the high oxidative stress of the tumor microenvironment, more and more researchers have been devoted to reactive oxygen species (ROS)-responsive nanodrug delivery systems for anticancer therapy. Herein, a ROS-responsive moiety, thioacetal, was synthesized, and cinnamaldehyde (CA) was introduced in the polymer chain to trigger the generation of ROS to expect the enhancement of the ROS-responsive effect. The poly(ester-thioacetal) mPEG2k-b-(NTA-HD)12 polymer, its self-assembled micelles, and the ROS-responsive behavior were characterized by 1H NMR and DLS. The anticancer drug doxorubicin (DOX) was adopted to prepare DOX-loaded poly(ester-thioacetal) micelles. The intracellular ROS detection indicated that the mPEG2k-b-(NTA-HD)12 polymer could degrade via the high concentration of ROS in cancer cells, and the released CA stimulated mitochondria to regenerate additional ROS. The flow cytometry results indicated that the ROS-responsive polymeric micelles showed faster cellular uptake compared to the control mPEG2k-b-PCL5k micelles. The ROS responsive DOX/mPEG2k-b-(NTA-HD)12 micelles exhibited much better anticancer efficiency on both 4T1 and HeLa cancer cells than DOX/mPEG2k-b-PCL5k micelles.