Engineering Multiresponsive Alginate/PNIPAM/Carbon Nanotube Nanocomposite Hydrogels as On‐Demand Drug Delivery Platforms

Abstract Second near‐infrared (NIR‐II) responsive hydrogels have shown significant potential in biomedical applications due to their excellent remote actuation property and the high tissue penetrations of the NIR‐II light. Nevertheless, hydrogels with a single NIR‐II light response may not meet the diverse requirements and complex conditions of clinical applications. Here, a novel multi‐responsive nanocomposite hydrogel with enhanced suitability for controlled drug release is developed. This nanocomposite hydrogel is constructed by combining alginate dialdehyde (ADA), polyethyleneimine (PEI), poly(N‐isopropylacrylamide) (PNIPAM), and phenylboronic acid‐modified polyethyleneimine (PBA‐PEI) functionalized multi‐walled carbon nanotubes (PP‐CNT) through the formation of dynamic covalent bonds (i.e., imine bonds and boronate ester bonds), forming ADA/PEI/PNIPAM/PP‐CNT (APN/PP‐CNT) hydrogel. PNIPAM is incorporated into the hydrogel network to facilitate drug release triggered by its aggregation when subjected to the high temperatures produced by NIR‐II light irradiation. The dynamic covalent bonds and CNT in the network provide the APN/PP‐CNT nanocomposite hydrogels with responsiveness to multiple stimuli, including pH, hydrogen peroxide, temperature, and NIR‐II light. The APN/PP‐CNT nanocomposite hydrogel performs effective NIR‐II light responsiveness in both in vitro and in vivo drug release, highlighting its potential as a promising drug delivery platform.