A novel medically imageable intelligent cellulose nanofibril-based injectable hydrogel for the chemo-photothermal therapy of tumors

The design of injectable hydrogels with excellent biocompatibility, medical imaging, and antitumor activity to improve the therapeutic efficiency on tumor tissues and to reduce toxic side effects is very important in clinical practice. A novel medically imageable pH-, temperature- and NIR- intelligent cellulose nanofibril (TOCNF)-based injectable hydrogel was designed using pH-, and temperature-responsive TOCNF as the carrier, citric-acid-stabilized Prussian blue nanoparticles (PBNPs) as the contrast agent and photothermal switch, and doxorubicin (DOX) as the chemotherapeutics agent. The hydrogel possessed a nanocage structure and a 3D network structure, which allowed a high loading capacity of PBNPs (2 mg/g) and DOX (415 mg/g). The PBNPs stabilized on TOCNF through electrostatic interactions and hydrogen bond could aid medical magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). Interestingly, the temperature, pH, and NIR tri-stimuli-responsive intelligent switches, inspired by the mimosa leaf, contributed to the controllable sustained DOX release property of the hydrogel. Therefore, in vivo bimodal MRI/PAI and tumor therapy results showed that the previously prepared hydrogel could be ideal for the rapid diagnosis and chemo-photothermal therapy in the clinical treatment of tumors.