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.

Pyroelectric Catalysis-Based "Nano-Lymphatic" Reduces Tumor Interstitial Pressure for Enhanced Penetration and Hydrodynamic Therapy.

Because of the deficiency of lymphatic reflux in the tumor, the retention of tumor interstitial fluid causes aggravation of the tumor interstitial pressure (TIP), which leads to unsatisfactory tumor penetration of nanomedicine. It is the main inducement of tumor recurrence and metastasis. Herein, we design a pyroelectric catalysis-based "Nano-lymphatic" to decrease the TIP for enhanced tumor penetration and treatments. It realizes photothermal therapy and decomposition of tumor interstitial fluid under NIR-II laser irradiation after reaching the tumor, which reduces the TIP for enhanced tumor penetration. Simultaneously, reactive oxygen species generated during the pyroelectric catalysis can further damage deep tumor stem cells. The results indicate that the "Nano-lymphatic" relieves 52% of TIP, leading to enhanced tumor penetration, which effectively inhibits the tumor proliferation (93.75%) and recurrence. Our finding presents a rational strategy to reduce TIP by pyroelectric catalysis for enhanced tumor penetration and improved treatments, which is of great significance for drug delivery.