Downregulation of the Tumor Interstitial Fluid Pressure to Boost Intratumoral Penetration and Hydrodynamic Therapy via CaO2-Based Ru Nanozymes

The high interstitial fluid pressure at the tumor tissue is a key factor that hinders the deep penetration of nanomedicines into the tumor and affects the therapeutic effect. Herein, we designed a CaO2-based Ru nanozyme to efficiently consume the tumor interstitial fluid and enhance deep tumor penetration as well as treatment. CaO2/Ru-PDA-HA (CRPH) reached tumors via hyaluronic acid (HA)-mediated tumor targeting. Under 808 nm laser irradiation, CRPH pyrolyzed and released CaO2 and Ru, and then CaO2 would consume H2O to produce O2 and H2O2 for reducing the tumor interstitial fluid volume to promote the tumor penetration of medicines. Meanwhile, Ru nanoparticles with good peroxidase activity can decompose H2O2 to generate cytotoxic •OH. Therefore, photothermal and ROS synergistic therapy damaged deep tumor stem cells. The results showed that the relative tumor interstitial pressure was reduced to 56.34%, and the tumor inhibition rate was 99.67%. The design provides a synergetic hydrodynamic therapy strategy for enhancing the deep penetration of nanomedicines and boosting the antitumor effect.