Figure 1.

An overview highlighting the design principles for prodrug-based nanomedicine. (a) Schematic of Molecular-graphics illustration of nanostructures formed from the prodrug strategy. Most prodrug strategies require a functional group on the parent drug. The selected prodrug approach is dictated by the liability of the drug that needs to be overcome by the prodrug strategy. (b) Linkage strategies for the most common functional groups found on parent drugs and representative stimuli-responsive linkers. Hydrazone conjugates can be converted to the active drug form in acidic environments. Dithiol linkages are sensitive to redox potential and easily cleaved in the presence of GSH. PVGLIG oligopeptide is selectively cleaved by matrix metalloproteinases (MMPs). (c) Release mechanisms for combination linkers. The choice of degradable linker and release mechanism of free drug from the prodrug can have a significant impact on the drug’s efficacy.