2. Academic Validation
  3. Topology regulation of nanomedicine for autophagy-augmented ferroptosis and cancer immunotherapy

Topology regulation of nanomedicine for autophagy-augmented ferroptosis and cancer immunotherapy

  • Sci Bull (Beijing). 2023 Jan 15;68(1):77-94. doi: 10.1016/j.scib.2022.12.030.
Ruizhi Hu 1,  Chen Dai 1,  Xinyue Dai 2,  Caihong Dong 3,  Hui Huang 2,  Xinran Song 4,  Wei Feng 2,  Li Ding 5,  Yu Chen 6,  Bo Zhang 7
Affiliations

Affiliations

  • 1 Department of Ultrasound, Shanghai East Hospital, Tongji University, Shanghai 200120, China.
  • 2 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, China.
  • 3 Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 4 Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai 200072, China.
  • 5 Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Education Institute, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, Tongji University Cancer Center, School of Medicine, Tongji University, Shanghai 200072, China. Electronic address: [email protected].
  • 6 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai 200444, China. Electronic address: [email protected].
  • 7 Department of Ultrasound, Shanghai East Hospital, Tongji University, Shanghai 200120, China. Electronic address: [email protected].
PMID: 36621435 DOI: 10.1016/j.scib.2022.12.030
Abstract

Iron accumulation and lipid peroxidation form the basis of Ferroptosis, potentially circumventing the limitations of Apoptosis in Cancer treatment. Owing to the lack of potent Ferroptosis inducers, the development of efficient ferroptosis-based therapeutic agents and protocols against cancers is highly challenging. Inspired by the topological effect of nanoparticles in modulating cellular function/status, a specific tetrapod ferroptosis-inducer iron-palladium (FePd) nanocrystal was rationally engineered for physically activated autophagy-augmented Ferroptosis and enhanced Cancer Immunotherapy. Specifically, the tetrapod FePd nanocrystal featured strong peroxidase-/glutathione oxidase-mimicking bioactivities, which promoted Cancer cell Ferroptosis. The special spiky morphology and nanostructure of the FePd nanocrystal simultaneously induced Autophagy, which augmented Ferroptosis in Cancer cells and triggered the release of inflammatory cytokines in macrophages for strengthening anti-PD-L1-antibody mediated immunotherapy, synergistically achieving the maximal antineoplastic effect in three tumor-bearing animal models. This unique physical activation strategy for efficient Cancer treatment via precise morphological tuning represents a paradigm for nanomedicine design for efficient tumor treatment.

Keywords

Autophagy; FePd; Ferroptosis; Immunotherapy; Spiky morphology; Topology modulation.

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