Affiliation:
1. Department of Pharmaceutical Sciences College of Pharmacy Oregon State University Portland OR 97201 USA
2. Department of Radiation Medicine School of Medicine Oregon Health & Science University Portland OR 97201 USA
3. Department of Cell Developmental and Cancer Biology School of Medicine Oregon Health & Science University Portland OR 97201 USA
4. Department of Chemistry Portland State University Portland OR 97201 USA
Abstract
AbstractRecent preclinical and clinical studies have highlighted the improved outcomes of combination radiotherapy and immunotherapy. Concurrently, the development of high‐Z metallic nanoparticles as radiation dose enhancers has been explored to widen the therapeutic window of radiotherapy and potentially enhance immune activation. In this study, folate‐modified hafnium‐based metal–organic frameworks (HfMOF‐PEG‐FA) are evaluated in combination with imiquimod, a TLR7 agonist, as a well‐defined interferon regulatory factor (IRF) stimulator for local antitumor immunotherapy. The enhancement of radiation dose deposition by HfMOF‐PEG‐FA and subsequent generation of reactive oxygen species (ROS) deregulates cell proliferation and increases apoptosis. HfMOF‐PEG‐FA loaded with imiquimod (HfMOF‐PEG‐FA@IMQ) increases DNA double‐strand breaks and cell death, including apoptosis, necrosis, and calreticulin exposure, in response to X‐ray irradiation. Treatment with this multipronged therapy promotes IRF stimulation for subsequent interferon production within tumor cells themselves. The novel observation is reported that HfMOF itself increases TLR7 expression, unexpectedly pairing immune agonist and receptor upregulation in a tumor intrinsic manner, and supporting the synergistic effect observed with the γH2AX assay. T‐cell analysis of CT26 tumors following intratumoral administration of HfMOF‐PEG‐FA@IMQ with radiotherapy reveals a promising antitumor response, characterized by an increase in CD8+ and proliferative T cells.
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献