“…Herein we describe a novel concentration-sensitive platform approach to prodrug activation based on controls by reaction kinetics using bioorthogonal click chemistry, which has been applied in prodrug preparation with excellent success. 12 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 Ideally, one would like to use linker chemistry that tethers the active drug to the targeting molecule in a stable fashion, and allow for selective cleavage at the desired site of action. 20 , 26 , 27 , 28 , 29 Through the use of click chemistry and the concept of co-localization, 30 , 31 the linker can be very stable until enrichment-triggered release (ETR).…”