An alternative concept to achieve signal-reversible prodrugs was introduced by Pillow and coworkers. The authors developed a drug delivery platform that combined a self-immolative spacer together with tertiary or heteroaryl amine drugs to form quaternary ammonium conjugates, which could be connected to a carrier protein. Here, a generic, scalable and straightforward coupling strategy of linker and drug molecules for the development of signalresponsive prodrug carriers would be highly advantageous.