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 CaO 2 -based Ru nanozyme to efficiently consume the tumor interstitial fluid and enhance deep tumor penetration as well as treatment. CaO 2 /Ru-PDA-HA (CRPH) reached tumors via hyaluronic acid (HA)-mediated tumor targeting. Under 808 nm laser irradiation, CRPH pyrolyzed and released CaO 2 and Ru, and then CaO 2 would consume H 2 O to produce O 2 and H 2 O 2 for reducing the tumor interstitial fluid volume to promote the tumor penetration of medicines. Meanwhile, Ru nanoparticles with good peroxidase activity can decompose H 2 O 2 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.