Fast Transport and Transformation of Biomacromolecular Substances via Thermo‐Stimulated Active “Inhalation–Exhalation” Cycles of Hierarchically Structured Smart pNIPAM–DNA Hydrogels

Abstract Although smart hydrogels hold great promise in biosensing and biomedical applications, their response to external stimuli is governed by the passive diffusion‐dependent substance transport between hydrogels and environments and within the 3D hydrogel matrices, resulting in slow response to biomacromolecules and limiting their extensive applications. Herein, inspired by the respiration systems of organisms, an active strategy to achieve highly efficient biomolecular substance transport through the thermo‐stimulated “inhalation–exhalation” cycles of hydrogel matrices is demonstrated. The cryo‐structured poly(N‐isopropylacrylamide) (pNIPAM)–DNA hydrogels, composed of functional DNA‐tethered pNIPAM networks and free‐water‐containing macroporous channels, exhibit thermally triggered fast and reversible shrinking/swelling cycles with high‐volume changes, which drive the formation of dynamic water stream to accelerate the intake of external substances and expelling of endogenous substances, thus promoting the functional properties of hydrogel systems. Demonstrated by catalytic DNAzyme and CRISPR‐Cas12a‐incorporating hydrogels, significantly enhanced catalytic efficiency with up to 280% and 390% is achieved, upon the introduction of active “inhalation–exhalation” cycles, respectively. Moreover, remotely near‐infrared (NIR)‐triggering of “inhalation–exhalation” cycles is achieved after the introduction of NIR‐responsive MXene nanosheets into the hydrogel matrix. These hydrogel systems with enhanced substance transport and transformation properties hold promise in the development of more effective biosensing and therapeutic systems.