Adaptable behavior such as triggered disintegration affords a broad scope and utility for (bio)materials in diverse applications in materials science and engineering. The impact of such materials continues to grow due to the increased importance of environmental considerations as well as the increased use of implants in medical practices. However, examples of such materials are still few. In this work, we engineer triggered liquefaction of hydrogel biomaterials in response to internal, localized heating, mediated by near-infrared light as external stimulus. This adaptable behavior is engineered into the readily available physical hydrogels based on poly(vinyl alcohol), using gold nanoparticles or an organic photothermal dye as heat generators. Upon laser light irradiation, engineered biomaterials underwent liquefaction within seconds. Pulsed laser light irradiation afforded controlled, on-demand release of the incorporated cargo, successful for small molecules as well as proteins (enzymes) in their biofunctional form.

Nanozymes can mimic the activities of diverse enzymes, and this ability finds applications in analytical sciences and industrial chemistry, as well as in biomedical applications. Among the latter, prodrug conversion mediated by nanozymes is investigated as a step toward site-specific drug synthesis, to achieve localized therapeutic effects. In this work, we investigated a ceria nanozyme as a mimic to phosphatase, to mediate conversion of phosphate prodrugs into corresponding therapeutics. To this end, the substrate scope of ceria as a phosphatase mimic was analyzed using a broad range of natural phosphor­(di)­esters and pyrophosphates. Knowledge of this scope guided the selection of existing phosphate prodrugs that can be converted by ceria into the corresponding therapeutics. “Extended scaffold phosphates” were engineered using self-immolative linkers to accommodate a prodrug design for amine-containing drugs, such as monomethyl auristatin E. Phosphate prodrugs masked activity of the toxin, whereas prodrug conversion mediated by the nanozyme restored drug toxicity, which was validated in mammalian cell culture. The main novelty of this work lies in the rational pairing of the ceria nanozyme with the existing and the de novo designed “extended scaffold” phosphate prodrugs toward their use in nanozyme–prodrug therapy based on the defined nanozyme substrate scope.