MnO2 Nanoflowers Induce Immunogenic Cell Death under Nutrient Deprivation: Enabling an Orchestrated Cancer Starvation‐Immunotherapy. Issue 4 (31st December 2020)

• Record Type: Journal Article
• Authors: Yang, Yannan; Gu, Zhengying; Tang, Jie; Zhang, Min; Yang, Yang; Song, Hao; Yu, Chengzhong
• Is Part Of: Advanced science. Volume 8:Issue 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-31
• Subjects: autophagy -- immunogenic cell death -- immunotherapy -- MnO2 nanoparticles; Science -- Periodicals; 505
• DOI: 10.1002/advs.202002667
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: MnO2 nanoparticles have been widely employed in cancer immunotherapy, playing a subsidiary role in assisting immunostimulatory drugs by improving their pharmacokinetics and/or creating a favorable microenvironment. Here, the stereotype of the subsidiary role of MnO2 nanoparticles in cancer immunotherapy is challenged. This study unravels an intrinsic immunomodulatory property of MnO2 nanoparticles as a unique nutrient‐responsive immunogenic cell death (ICD) inducer, capable of directly modulating immunosurveillance toward tumor cells. MnO2 nanoflowers (MNFs) constructed via a one pot self‐assembly approach selectively induce ICD to nutrient‐deprived but not nutrient‐replete cancer cells, which is confirmed by the upregulated damage associated molecular patterns in vitro and a prophylactic vaccination in vivo. The underlying mechanism of the MNFs‐mediated selective ICD induction is likely associated with the concurrently upregulated oxidative stress and autophagy. Built on their unique immunomodulatory properties, an innovative nanomaterials orchestrated cancer starvation‐immunotherapy is successfully developed, which is realized by the in situ vaccination with MNFs and vascular disrupting agents that cut off intratumoral nutrient supply, eliciting potent efficacy for suppressing local and distant tumors. These findings open up a new avenue toward biomedical applications of MnO2 materials, enabling an innovative therapeutics paradigm with great clinical significance. Abstract : An intrinsic immunomodulatory property of MnO2 flowers in regulating the immunogenicity of cancer cells in a nutrient‐responsive manner is unraveled. This finding leads to an innovative nanomaterials orchestrated cancer starvation‐immunotherapy by co‐administering MnO2 nanoflowers and vascular disrupting agents that suspend intratumoral nutrient supply, realizing an "in situ vaccination" approach with remarkable antitumor performance in suppressing local and distant tumors.