International audienceThe development of flexible drug delivery systems that can be tuned as a function of the drug to bedelivered and of the target disease is crucial in modern medicine. For this aim, novel amphiphilic poly-(e-caprolactone)-g-poly(ethylene glycol) (PCL-g-PEG) copolymers with well-controlled design weresynthesized by thiol–yne photochemistry. The grafting density and the copolymer amphiphilicity wereeasily controlled via the reaction parameters: concentration, reaction time, PEG length and the molarratio between PCL and PEG or the photoinitiator in the reaction mixture. The self-assembling behaviorof the copolymers was studied and a correlation between the composition of PCL-g-PEG and thenanoaggregate diameter sizes (28 to 73 nm) and critical aggregation concentrations (1.1 to 4.3 mg L1)was found. The influence of copolymer amphiphilicity on the drug loading was evaluated with variousdrugs including anticancer drugs (paclitaxel, ABT-199), drugs to overcome multidrug resistance incancer cells (curcumin, elacridar), an anti-inflammatory drug (dexamethasone) and an antibacterial drug(clofazimine). Finally, the influence of amphiphilicity on curcumin release and toxicity towards MCF-7cancer cell lines was studied. The impact of the grafting density, PEG length and the overall EG/CL ratiois discussed in detail. Curcumin loaded PCL-g-PEG with lower EG/CL ratios and shorter PEG chainsshowed higher toxicity compared to their more hydrophilic counterparts