Intracellular coassembly boosts the anti-inflammation capacity of dexamethasone

Dexamethasone (Dex) is one of the essential medicines used to treat inflammation diseases but an overdose of Dex leads to severe adverse effects. The development of a new strategy to boost the anti-inflammation efficacy of Dex is, therefore, important but remains challenging. Herein, by employing an enzyme-instructed self-assembly system, we developed an intracellular coassembly strategy to boost the anti-inflammation efficacy of Dex. Under the catalysis of alkaline phosphatase (ALP), the hydrogelator precursor Nap-Phe-Phe-Tyr(H₂PO₃)-OH (1p) self-assembled to form Gel 1 but dexamethasone sodium phosphate (Dp) only yielded Dex precipitates. However, subjecting equivalent amounts of 1p and Dp together to ALP-triggered coassembly was found to result in the formation of Gel 2. Cell experiments indicated that intracellular ALP-triggered coassembly of Dp with 1p extensively boosted the anti-inflammation efficacy of Dex on two types inflammatory cell models. We envision that, in the near future, our strategy of intracellular coassembly could be widely employed to boost the therapeutic effects of more drugs, while in the meantime used to alleviate the undesired adverse effects of these drugs.