Decrease in Tumor Interstitial Pressure for Enhanced Drug Intratumoral Delivery and Synergistic Tumor Therapy

Currently, one of the main reasons for the ineffectiveness of tumor treatment is that the abnormally high tumor interstitial pressure (TIP) hinders the delivery of drugs to the tumor center and promotes intratumoral cell survival and metastasis. Herein, we designed a "nanomotor" by in situ growth of Ag₂S nanoparticles on the surface of ultrathin WS₂ to fabricate Z-scheme photocatalytic drug AWS@M, which could rapidly enter tumors by splitting water in interstitial liquid to reduce TIP, along with O₂ generation. Moreover, the O₂ would be further converted to reactive oxygen species (ROS), accompanied by increased local temperature of tumors, and the combination of ROS with thermotherapy could eliminate the deep tumor cells. Therefore, the "nanomotor'' could effectively reduce the TIP levels of cervical cancer and pancreatic cancer (degradation rates of 40.2% and 36.1%, respectively) under 660 nm laser irradiation, further enhance intratumor drug delivery, and inhibit tumor growth (inhibition ratio 95.83% and 87.61%, respectively), and the related mechanism in vivo was explored. This work achieves efficiently photocatalytic water-splitting in tumor interstitial fluid to reduce TIP by the nanomotor, which addresses the bottleneck problem of blocking of intratumor drug delivery, and provides a general strategy for effectively inhibiting tumor growth.