Proteases are another large family of enzymes that can be targeted for the selective cleavage of polymer-drug linkers, due to their abundance in the body 129 and their involvement in numerous biological phenomena such as cell differentiation 130 or angiogenesis. By hydrolyzing amide bonds, protease activity are essential in normal physiology but can also been dysregulated and implicated in the development of tumors. Even if not directly connected to the drug, inserting peptide sequences into polymer structures is a promising approach for generating protease-sensitive polymer prodrugs by RDRP. A typical example is to use the Glycine-Phenylalanine-Leucine-Glycine (GFLG) peptide (Figure ), which is sensitive to the protease cathepsin B and remains stable in plasma, allowing cleavage after endocytosis. One clever strategy for inserting the GFLG peptide into RDRP polymer prodrugs is to use a difunctional GFLG-based RAFT agent, which ensures the presence of the peptide in the middle of the polymer backbone after divergent RAFT polymerization. This was applied to the synthesis of (poly(N-(1,3-dihydroxypropan-2-yl) methacrylamide)-co-methacrylamide-hyd-Dox) 2 -GFLG polymer prodrugs (Figure ), which self-assembled into micelles of 21 nm (Figure ). This enabled the possibility of a combined therapy that suppressed tumor growth in 4T1 tumorbearing mice.