Wang H, Monroe M, Leslie F, Flexner C, Cui H. Supramolecular nanomedicines through rational design of self-assembling prodrugs. Trends Pharmacol Sci. 2022 Jun;43(6):510-521. doi: 10.1016/j.tips.2022.03.003. Epub 2022 Apr 19. PMID: 35459589; PMCID: PMC9106924.
Advancements in the development of nanomaterials have led to the creation of a plethora of functional constructs as drug delivery vehicles to address many dire medical needs. The emerging prodrug strategy provides an alternative solution to create nanomedicines of extreme simplicity by directly using the therapeutic agents as molecular building blocks. This review outlines different prodrug-based drug delivery systems, highlights the advantages of the prodrug strategy for therapeutic delivery, and demonstrates how combinations of different functionalities—such as stimuli responsiveness, targeting propensity, and multidrug conjugation—can be incorporated into designed prodrug delivery systems. Furthermore, we discuss the opportunities and challenges facing this rapidly growing field.