Surprisingly, an early burst release of Lapa was observed at very low ROS levels, probably due to the non-covalent interactions between Lapa and the polymer chains. In vitro studies have demonstrated a significant ROS production induced by Lapa in 4T1 cancer cells as well as a synergistic activity with higher cytotoxicity of dual-loaded micelles compared to the physical mixture of the two drugs. In vivo administration of dual-loaded micelles in 4T1 tumorbearing mice confirmed their specific accumulation at the tumor site, resulting in enhanced antitumor efficacy and in suppression of tumor growth, without systemic toxicity. Interestingly, they could be formulated into 69 nm stable micelles loaded with Dox (Figure ), with a loading in Cpt and Dox of 18.9 wt % and 5.2 wt %, respectively. Reductive environment (10 mM GSH) led to significant release of Cpt (75 % after 48 h), while slightly acidic conditions (pH 5) promoted release of Dox (70 % after 72 h), due to protonation of DPA units, creating a more hydrophilic environment (Figure ). Cell viability assays on HeLa and MCF-7 cells demonstrated synergistic effect of the drug combination compared to Dox-free micelles, as well as good blood compatibility.