Affiliation:
1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine School of Public Health Xiamen University Xiamen 361102 China
2. State Key Laboratory of Cellular Stress Biology Innovation Center for Cell Biology School of Life Sciences Xiamen University Xiamen 361102 China
3. School of Medicine Xiamen University Xiamen 361102 China
Abstract
AbstractIt 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 is developed. 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 are rationally integrated. Notably, the Fenton‐like activity significantly enhances Ru‐TePt nanorods sonosensitization, thus provoking stronger oxidative stress to kill cells directly. Meanwhile, immunogenic cell death is 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 reactive oxygen species‐triggered antitumor immune response. The experimental results in vitro and in vivo reveal that the Ru‐TePt@siRNA‐MVs nanosystems can 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.
Funder
National Natural Science Foundation of China
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
8 articles.
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