(i) the ester bond from HEMA-ester-Ibu monomer prodrug and (ii) the benzoic-imine bond at the junction of the two polymer blocks. As a proof of concept, Dox was physically encapsulated into the nanoparticle core, with an encapsulation efficiency of 33 %. Cleavage of the benzoicimine groups at pH 5 led to nanoparticle disassembly and greater Dox release compared to physiological conditions (55 vs. 35 % after 10 h, respectively). The release of ibuprofen was also accelerated under acidic conditions due to the nanoparticle disassembly that promoted cleavage of ester linkers. Cell assays on B16 cells demonstrated significant ibuprofen activity after ester cleavage and similar in vivo anti-tumor activity than free Dox in B16 tumor-bearing mice, but without systemic toxicity.