Consistent with our fluorophore-based measurements, we observed complete (>99%) iTCO-release across all caged drugs with both Tz, drama=cally faster and higher yielding than the rTCO controls. iTCO-Dox exhibited immediate uncaging with both Tz, matching the kine=cs of primary amine release observed with the fluorescent probe iTCO-AF594 (Fig. ). Immediate iTCO-MMAE cleavage was also triggered by Pyr2 (15), whereas MeBAm (13) elicited a progressive release profile; the differen=al kine=cs of the two drugs may reflect Tz-specific subtle=es of primary vs secondary amine leaving groups, a subject of ongoing inves=ga=on. The data for CA4 reflect the expected mul=step-process: an ini=al fast iTCO-release, producing DMEDA-CA4, followed by the inherently slower self-immola=on of DMEDA-CA4 to yield the free drug , with both Tz triggers reaching comple=on.