Assessing its chemical capabili=es in a biological context, we find that iTCO is par=cularly stableremaining more than 97% intact aUer 24 hours at physiological temperature in human plasma-and highly performant in complex environments, achieving efficient extra-and even intracellular prodrug ac=va=on, as well as complete intravital cleavage at remarkably low Tz concentra=ons. These findings underscore the poten=al of iTCO for a wide range of advanced applica=ons in diagnos=cs and therapy. With its combina=on of next-level chemical performance and excellent stability, we are convinced that iTCO opens the door to the next chapter of bioorthogonal explora=on across the full biological spectrum-from cells to =ssues to en=re organisms.