Tumor microenvironment responsive-multifunctional nanocomposites knotted injectable hydrogels for enhanced synergistic chemodynamic and chemo-photothermal therapies

Multifunctional nanomedicine has offered a promising strategy for effective anticancer therapy owing to its versatile capabilities. However, the systematic precise delivery still remains intractable challenge because of the existence of multi-staged biological barriers after intravenous administration. Herein, to address this issue, injectable and TME-responsive nanocomposite hydrogels were developed for localized and synergistic cancer therapy. The nanocomposite hydrogels (Au NBPs&Pt NCs@DOX gel) were synthesized via the formation of metal-sulfur bonds between 4arm-PEG-thiol and Au nanobipyramids or Pt nanoclusters with the DOX encapsulation. The hydrogel exhibited rapid gelation and excellent injectability. Attributed to the high absorbance of Au NBPs, the nanocomposite hydrogels revealed superior photothermal effect under NIR irradiation, which the DOX release was also regulated by NIR laser. In addition, the catalase- and peroxidase-like activities of Pt NCs were validated to convert endogenous H2O2 into ROS and O2 in situ to achieve chemodynamic therapy (CDT) and alleviate the hypoxic microenvironment. Simultaneously, catalytic therapy combined with NIR irradiation exhibited strongest inhibition to the growth of 4T1 tumor in vitro and in vivo. Thus, this study provided a new strategy for TME remodeling and local combination therapies of different therapeutic agents.