Multistage-Targeted Gold/Mesoporous Silica Nanocomposite Hydrogel As In Situ Injectable Drug Release System For Chemophotothermal Synergistic Cancer Therapy

Injected tissue-affinity drug-laden nanocomposite hydrogels are promising materials for tumor therapy owing to both maintenance and release of drug in situ. In this study, a hyaluronic acid (HA) hydrogel covalently embedded with doxorubicin loaded and triphenylphosphine (TPP) modified core-shell gold mesoporous silica nanoparticles is fabricated as a local drug-delivery system for sustained stomach cancer treatment. HA has excellent biocompatibility as the main component of the extracellular matrix and specific affinity toward the CD44-overexpressed cancer cell. TPP is a classic targeted feature of mitochondria. After in situ injection, the hydrogel patch can adhesively land at the tumor site, and it exerts further control through dissociation because of the degradation of hyaluronidase around the solid tumor, leading to the release of core-shell gold mesoporous silica nanoparticles conjugated with TPP and HA fragment. These particles can selectively attack cancer cells followed by entering into mitochondria. Additionally, the core gold nanoparticle mediates the transformation of near-infrared radiation into thermal energy, enhancing the release of chemotherapy drugs and heat-induced cellular injury. This in situ, chemophotothermal combination hydrogel is verified to have an excellent therapeutic effect on gastric tumor through in vitro and in vivo experiments, providing the potential to serve as a multistage-target drug-delivery platform for chemophotothermal synergistic cancer therapy.