formation. The resulting P(MPC-co-POEGMA-Bz-imine-Dox) copolymer prodrug was then functionalized at the chain-end with folic acid (FA) using click chemistry for the targeting of tumor-overexpressed FA receptors. Prodrug nanoparticles of 140 nm diameter with high Dox loadings (up to 28 wt %) exhibited selective release of Dox and colloidal disassembly at pH 5, as shown by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The FA-decorated nanoparticles led to greater internalization in HeLa cells compared to their nontargeted counterparts. However, the cytotoxicity was rather similar with or without targeting ligand, which may be explained by a partial accessibility of FA to folic acid receptors. Interestingly, polymer prodrugs from RDRP can also combine two pH-sensitive modalities to better control the drug release kinetics and thus the therapeutic efficacy. This strategy seems particularly useful in cancer therapy, where the pH difference between cancer cells and healthy cells remains very small and difficult to exploit. hydrolysis of the imine groups that led to Dox release at pH < 5.5 (Figure ). Such dual pHresponsiveness led to a greater Dox release after 4 h at pH 5.5 (~80 %) than at pH 6.5 (~40 %) and at pH 7.4 (~10 %). They also exhibited significant cell internalization into HeLa cells at pH 5.5 compared to pH 6.5 (which was already greater than at pH 7.4), whereas the Dox-free micelles showed good cytocompatibility up to 10 mg.mL -1 . Other studies have reported dual pH-sensitive polymer prodrugs for the delivery of Dox using, for instance, β-cyclodextrin-star- The ester bond is also a widely-used drug linker to design polymer prodrugs by RDRP techniques (Figure ). It is usually obtained by condensation between hydroxyl and carboxylic acid groups and appeared to be a valuable polymer-drug linker because it can be cleaved by more than one stimuli including different pH conditions (acid and basic 87 ), metal ions via hydrolytic degradation, 88 or also the action of enzymes such as esterases and acid hydrolases. Such sensitivity to different stimuli may allow better control of drug release kinetics without complicating prodrug synthesis. Similarly to what has been shown with hydrazone and imine linkers, the acid-sensitivity can be selectively triggered when the polymer prodrugs reach specific cell compartments such as lysosomes or endosomes, where it is also frequent to find a variety of enzymes (as acid hydrolases and esterases) that could enhance intracellular ester bond cleavage. In addition, ester bonds are suitable for basic-catalyzed hydrolysis that could be relevant for achieving drug delivery to subcellular compartments such as mitochondria or peroxisomes, where the pH is slightly basic (~ 8-9 and acidic conditions (using ascorbic acid 7.5 mM and pH 5) showed reduction of oxoplatin to the platinum (II) complex, followed by gradual release of cisplatin. Release of oxoplatin also led to micelle disassembly due to the formation of a water-soluble PMAA block, which should induce better clearance of the polymer when administered in vivo. Interestingly, the largest micelles showed the highest cytotoxicity on OVCAR-3 (FR+) cells but not on A549 (FR-) cells, demonstrating the targeting efficiency.