Multicomponent Micelles with Boosted Stability of Iminoboronates

Multicomponent reactions (MCRs) enable efficient construction of multifunctional materials, with iminoboronate chemistry offering attractive pH and redox responsiveness for smart biomaterials. However, their poor kinetic stability under aqueous dilution and elevated CO2 levels limit biomedical applications. Herein, we address this challenge by embedding iminoboronate linkages within supramolecular assemblies, where nanoconfinement modulates their kinetic behaviors. The hydrophobic microenvironment of the supramolecular micellar core effectively restricts water accessibility to the iminoboronate moieties, converting the inherent kinetic instability into assembly-dependent and environment-regulated stability. By varying amine derivatives and natural polyphenols, a series of multicomponent supramolecular micelles were constructed. In cellular studies and postoperative skin cancer models, multifunctional micelles coloaded with doxorubicin and epigallocatechin gallate exhibited a synergistic therapeutic profile, effectively suppressing tumor recurrence while simultaneously promoting wound healing. This work establishes supramolecular confinement as a general strategy to stabilize kinetically labile MCR-derived linkages, expanding the biomedical potential of iminoboronate chemistry.