Injectable NIR-II-responsive nanocomposite hydrogels containing gold nanoparticle-decorated carbon nanotubes for controllable drug delivery and tumor therapy.

Injectable second near-infrared (NIR-II)-responsive nanocomposite hydrogels have emerged as promising biomaterials for tumor therapy due to their ability to achieve spatiotemporal control over drug release at the targeted site. Nevertheless, the clinical translation of these hydrogels is often hindered by the poor distribution and photothermal conversion effect of the photosensitizer within the hydrogel matrix. To address these challenges, an advanced NIR-II-responsive nanocomposite hydrogel is developed by functionalizing carbon nanotubes (CNTs) with gold nanoparticles (AuNPs) and hydrophilic surfaces, positioning them as effective photosensitizers and crosslinkers. The hydrophilic AuNP-decorated CNTs and polyethyleneimine (PEI) react with alginate dialdehyde (ADA) via dynamic imine and boronate ester bonds to construct the hydrogel network. The AuNPs also form coordination and electrostatic interactions with the polymeric network. Additionally, poly(N-isopropylacrylamide) (PNIPAM) is incorporated to impart thermal-responsiveness to the hydrogel matrix. Comprehensive investigations of the microstructures, properties, and controlled drug release behavior of the nanocomposite hydrogels are conducted. Notably, the nanocomposite hydrogel enables controlled release of hydrophilic drugs under NIR-II light exposure. In vivo studies further demonstrate their synergistic chemo-photothermal effectiveness in tumor treatment. Taken together, this work introduces a promising injectable NIR-II-responsive AuNP-decorated CNT-containing nanocomposite hydrogel as a versatile platform for precise drug delivery and effective tumor therapy. STATEMENT OF SIGNIFICANCE: This study presents an innovative injectable NIR-II-responsive nanocomposite hydrogel platform designed for precision tumor therapy through synergistic chemo-photothermal treatment. By engineering gold nanoparticle-functionalized carbon nanotubes with hydrophilic surfaces, the hydrogel addresses key limitations of conventional systems, including poor photosensitizer distribution and insufficient photothermal conversion efficiency. The unique incorporation of dynamic imine and boronate ester linkages, combined with thermal-responsive PNIPAM, enhances mechanical integrity, thermal sensitivity, and drug delivery control. Importantly, this work demonstrates that this hydrogel can spatiotemporally release 5-fluorouracil under NIR-II irradiation and achieve effective tumor ablation both in vitro and in vivo. This contribution significantly impacts the field of stimuli-responsive biomaterials and cancer theranostics by offering a robust, multifunctional, and translationally promising hydrogel platform.