Affiliation:
1. Department of Radiation Oncology Sun Yat‐sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine 651 Dongfeng Road East Guangzhou 510060 P. R. China
2. Department of Gastrointestinal Medical Oncology, Key Laboratory of Tumor Immunology in Heilongjiang Harbin Medical University Cancer Hospital Harbin 150001 P. R. China
3. Key Laboratory of Superlight Materials and Surface Technology Ministry of Education College of Materials Science and Chemical Engineering Harbin Engineering University Harbin 150001 P. R. China
4. Department of Neurosurgery First Affiliated Hospital of Harbin Medical University Harbin 150001 P. R. China
Abstract
AbstractImmunotherapy using an immune‐checkpoint blockade has significantly improved its therapeutic effects. CM‐272, which is a novel epigenetic inhibitor of G9a, induces immunogenic cell death (ICD) for recovering the sensitivity to anti‐PD‐1 antibodies; however, the efficacy of CM‐272 is greatly limited by promoting the transcription activity of HIF‐1α to form a hypoxic environment. Here, a Fe3+‐based nanoscale metal–organic framework (MIL‐53) is used to load CM‐272 (ultra‐high loading rate of 56.4%) for realizing an MIL‐53@CM‐272 nanoplatform. After entering bladder cancer cells, Fe3+ not only promotes the decomposition of H2O2 into O2 for O2‐compensated sonodynamic therapy but reduces the high level of glutathione in the tumor microenvironment (TME) for enhancing reactive oxygen species, including ferroptosis and apoptosis. MIL‐53 carriers can be degraded in response to the TME, accelerating the release of CM‐272, which helps achieve the maximum effectiveness in an O2‐sufficient TME by attenuating drug resistance. Furthermore, MIL‐53@CM‐272 enhances dendritic cell maturation and synergistically combines it with an anti‐programmed cell death protein 1 antibody during the study of immune‐related pathways in the transcriptomes of bladder cancer cells using RNA‐seq. This study presents the first instance of amalgamating nanomedicine with CM‐272, inducing apoptosis, ferroptosis, and ICD to achieve the “one arrow three eagle” effect.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Heilongjiang Province
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science