NIR/Thermoresponsive Injectable Self-Healing Hydrogels Containing Polydopamine Nanoparticles for Efficient Synergistic Cancer Thermochemotherapy.

Injectable and self-healing hydrogels with thermoresponsiveness as smart hydrogels displayed injectability, automatic healing, and phase and volume changes as well. Here, the thermoresponsive self-healing hydrogel was prepared via the formation of dynamic covalent enamine bonds between the amino groups in polyetherimide (PEI) and the acetoacetate groups in the four-armed star-shaped poly(2-(dimethylamino)ethyl methacrylate--2-hydroxyethyl methacrylate) modified with -butyl acetoacetate (-BAA), SP(DMAEMA--HEMA-AA). After adding polydopamine nanoparticles (PDA NPs), the SP(DMAEMA--HEMA-AA)/PEI/PDA-NP nanocomposite hydrogel presented phase change and volume shrinkage under near-infrared (NIR) irradiation. The thermoresponsive nanocomposite hydrogel loaded with the anticancer drug doxorubicin (DOX) could be injected into the 4T1 tumor by intratumoral injection. After NIR laser irradiation, the temperature of the hydrogel increased because of the photothermal effect of PDA NPs inducing local hyperthermia. Because the hydrophilicity-hydrophobicity transition of the hydrogel occurred, DOX molecules were squeezed out from the hydrogel at temperatures higher than its lower critical solution temperature (LCST) and the tumor cells suffered from internal stress from the shrunk hydrogel. The injectable nanocomposite hydrogel not only demonstrated the synergism of highly efficient thermochemotherapy but also showed the function of improving drug utilization and precise treatment to reduce the side effects of drugs.