Polymer prodrugs featuring redox-sensitivity have also been developed by the "grafting through" method due to the relative ease of inserting redox-sensitive groups between the drug and the monomer, such as disulfide and thioketal linkers. Similarly to Cpt, HSEMA has also been conjugated to the anticancer agent irinotecan (Ir) via establishment of a carbonate bond, to produce reducible star-like α-CD-P(HSEMA-SS-Ir-co-OEGMA) polymer prodrugs by copolymerization of HSEMA-SS-Ir and OEGMA from α-CD-Br ATRP (Figure ). They were able to self-assemble into 50 nm micelles of ~31 wt % drug loading, that remained stable in non-reductive conditions, whereas at high concentrations in GSH (10 mM), release of Ir reached 80 % after 120 h vs. < 15 % for 0 and 2 µM GSH (Figure ). Cytotoxicity assays on HeLa cells showed improved cytotoxicity of the polymer prodrugs compared to free Cpt (45 % vs. 25 % of cell viability, respectively). Similar results were obtained on MCF-7 cells, and hematology assays have demonstrated sufficient biocompatibility for other in vivo applications. disulfide-containing monomer. The obtained HEMA-SS-Cpt was copolymerized with OEGMA from a carboxylic acid-bearing ATRP initiator, aiming to increase the water solubility of the polymer prodrug while protecting Cpt from early degradation. The LHRH (Luteinizing Hormone-Releasing Hormone) targeting peptide was eventually grafted to the carboxylic acid chain end of HOOC-P(HEMA-SS-Cpt)-b-POEGMA polymer prodrugs to facilitate its cellular uptake by cancer cells that overexpressed LHRH receptors. The resulting 20 nm-micelles induced significant Cpt release, reaching 90 % after 24 h under 5 mM of DTT. The targeting properties of the polymer prodrug were evaluated on overexpressing LHRH receptor cell lines (A2780, IGROV-1, CACO-2), showing comparable cytotoxicity to that of free Cpt, conversely to the low cytotoxicity obtained on a LHRHR-negative cell line (CALU-3).