Figure 1.

Overview of modular prodrug design strategy. A self-immolative linker (gray) bridges three modular functional aspects of an inactive nontoxic prodrug: a bioorthogonally cleavable protective group (shown here in red as allyloxycarbonyl, alloc) that is removed upon exposure to a triggering agent, a nanoencapsulation anchor (shown here in green using an aliphatic C₁₆ chain), and the caged drug payload (blue). A bioorthogonal activating agent, here using Pd-NP based on the polymeric micellar encapsulation of PdCl₂(TFP)₂, leads to drug uncaging and activation in a spatiotemporally controlled manner.