LAUSR

It is an engaging program for tumor treatment that rationalizes the specific microenvironments, activation of suppressed immune system (immune resistance/escape reversion), and synergistic target therapy. Herein, a biomimetic nanoplatform that combines oxidative stress with genetic immunotherapy to strengthen the therapeutic efficacy was developed. We rationally integrated Ru-TePt nanorods, small interfering RNA (PD-L1 siRNA), and biomimetic cellular membrane vesicles with the targeting ability to design a multifunctional Ru-TePt@siRNA-MVs system. Notably, the Fenton-like activity significantly enhanced Ru-TePt nanorods sonosensitization, thus provoking stronger oxidative stress to kill cells directly. Meanwhile, immunogenic cell death (ICD) triggered to secrete numerous cytokines and activate T cells. The effective catalase characteristics of Ru-TePt enable the in-situ oxygen-producing pump to improve tumor oxygen level and coordinately strengthen the therapeutic effect of SDT followed. More importantly, anti-PD-L1-siRNA mediated immune checkpoint silence of the PD-L1 gene creates an environment conducive to activating cytotoxic T lymphocytes, synergistic with boosted ROS-triggered anti-tumor immune response. The experimental results in vitro and in vivo revealed that the Ru-TePt@siRNA-MVs nanosystems could effectively activate the oxidative stress-triggered immune response and inhibit PD-1/PD-L1 axis-mediated immune resistance. Consequently, this orchestrated treatment paradigm provides valuable insights for developing potential oxidative stress and genetic immunotherapy. This article is protected by copyright. All rights reserved.