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

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.