Palladium nanosheet-knotted injectable hydrogels formed via palladium‒sulfur bonding for synergistic chemo-photothermal therapy
Nanoparticle (NP)-based hydrogels that can introduce synergistic advantages to the novel three-dimensional scaffold have garnered much attention recently. However, the application of NP-crosslinked hydrogels still remains challenging due to the complicated procedures (including synthesis and/or modification of NPs) and the changed properties of NPs after gelation. Herein, a novel palladium nanosheet (Pd NS)-based hydrogel (Pd Gel) with Pd NSs as the crosslinkers was obtained by simply mixing Pd NSs with thiol-terminated four-arm polyethylene glycol (4arm-PEG-thiol). It was found that the formed Pd Gel was injectable, possibly due to the dynamic Pd−S bonds formed between Pd NSs and 4arm-PEG-thiol. In addition, compared with free Pd NSs, the Pd NSs within the hydrogel exhibited significantly higher stability. We have further demonstrated that the formed hydrogel could encapsulate the commonly used anticancer drug doxorubicin (DOX) to form DOX@Pd Gel for combined chemo-photothermal therapy. Particularly, Pd NSs with high absorption in the near-infrared (NIR) region could convert the energy of NIR laser into heat with high efficiency, which is beneficial for photothermal therapy. Moreover, DOX@Pd Gel could maintain a sustainable release of DOX and the NIR laser irradiation could accelerate this drug release process. Then, the explosively released DOX and the hyperthermia generated from Pd NSs under NIR laser irradiation acted in a synergistic way to realize the combined therapeutic effect of chemo-photothermal treatment. Finally, the in vivo anticancer effect and safety of the combined therapy were also verified by the tumor-bearing mouse model. Taken together, this work constructs a NP-crosslinked, NIR laser-activatable and injectable photothermal hydrogel via dynamic Pd−S bonding, and demonstrates that the hydrogel allows us to release DOX more precisely, eliminate tumor more effectively and inhibit tumor metastasis more persistently, which will advance the development of novel anticancer strategies.