substantiating the suggested mechanism of degradation and clearly demonstrating that physiological levels of ROS are sufficient to trigger drug release (cf. Figure and mass in Figure ). Surprisingly, the induction with LPS does not seem to be so decisive for the degradation of the particles, since we also find both fragments in the sample where we treat the cells only with P1 and no LPS (see Figure ). The uptake of particles alone seems to be sufficient to activate the macrophages and stimulate ROS production. Interestingly, we do not observe native Lenvatinib, but it should be noted that LC-MS analysis is limited to a fixed point in time and that the drug may have been metabolized or bound to form a larger complex. In view of our previous enzyme assay, which showed that the prodrug monomer 2 is also able to inhibit the target VEGFR2 receptor, our results corroborate that the polyimidazole-based nanoparticles represent an interesting drug delivery system that can be degraded by cells and that active Lenvatinib is released in this process (see Figure ).