Redox-responsive polymer prodrugs derived from the "grafting through" method can also target the tumoral environment by having cleavable chemical bonds between the drug and the monomer that are sensitive to reactive oxygen species (ROS), 164 which are often observed in cancer cells and play a key role in angiogenesis. The thioketal (tkl) bond is a representative example in this area (Figure ) as it is degraded through a self-immolative pathway when exposed to high levels of ROS. Similarly to disulfide-containing Cpt-monomers, Cpt was conjugated to 2-((2-((2-hydroxyethyl)thio)propan-2-yl)thio)ethyl methacrylate which contains a thioketal group between the methacrylate moiety and the drug (Figure ). Such monomer (MA-tkl-Cpt) was polymerized by RAFT from a PEG-based macro-RAFT agent, to give redoxresponsive polymer prodrug micelles of 48 nm in diameter. They were also able to physically encapsulate a second hydrophobic drug, ꞵ-lapachone (Lapa), known to specifically increase the ROS level in cancer cells, 168 with high encapsulation efficiency (98.5 %) and a loading in Lapa of 9 %. Such dual-drug micelles aimed to induce a ROS production via Lapa release followed by the ROS-mediated thioketal cleavage (Figure ), triggering the Cpt release. In absence of ROS, the Cpt release remained negligible, avoiding a toxic release in healthy tissues, whereas high levels of ROS (1 mM H 2 O 2 + Fe 2+ ) led to enhanced release of Cpt.