Defect self-assembly of metal-organic framework triggers ferroptosis to overcome resistance

Haibao Peng; Xingcai Zhang; Peng Yang; Jiaxu Zhao; Wei Zhang; Nianping Feng; Wuli Yang; Jing Tang

doi:10.1016/j.bioactmat.2021.12.018

Defect self-assembly of metal-organic framework triggers ferroptosis to overcome resistance

Bioact Mater. 2021 Dec 30:19:1-11. doi: 10.1016/j.bioactmat.2021.12.018. eCollection 2023 Jan.

Authors

Haibao Peng^{1

2

3}, Xingcai Zhang⁴, Peng Yang⁵, Jiaxu Zhao¹, Wei Zhang¹, Nianping Feng³, Wuli Yang², Jing Tang⁶

Affiliations

¹ Institute for Translational Brain Research, Fudan University, Shanghai, 200032, China.
² State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200438, China.
³ Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁴ School of Engineering, Massachusetts Institute of Technology, Cambridge, MA, 02139, United States.
⁵ Engineering Research Center of Molecular- and Neuro-imaging of Ministry of Education, School of Life Science and Technology, Xidian University, 710126, China.
⁶ Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, United States.

Abstract

The emergence of multidrug treatment resistance presents a hurdle for the successful chemotherapy of tumours. Ferroptosis, resulting from the iron-dependent accumulation of lipid peroxides, has the potential to reverse multidrug resistance. However, simultaneous delivery of the iron sources, ferroptosis inducers, drugs, and enhanced circulation carriers within matrices remains a significant challenge. Herein, we designed and fabricated a defect self-assembly of metal-organic framework (MOF)-red blood cell (RBC) membrane-camouflaged multi-drug-delivery nanoplatform for combined ferroptosis-apoptosis treatment of multidrug-resistant cancer. Ferroptosis and chemotherapeutic drugs are embedded in the centre of the iron (III)-based MOF at defect sites by coordination with metal clusters during a one-pot solvothermal synthesis process. The RBC membrane could camouflage the nanoplatform for longer circulation. Our results demonstrate that this defect self-assembly-enabled MOF-membrane-camouflaged nanoplatform could deplete the glutathione, amplify the reactive oxidative species oxidative stress, and enable remarkable anticancer properties. Our work provides an alternative strategy for overcoming multidrug resistance, which could regulate the fluidity and permeability of the cell membrane by ferroptosis to downregulate of P-glycoprotein protein expression by ferroptosis. This defect self-assembly-enabled MOF-membrane-camouflaged multi-drug-delivery nanoplatform has great therapeutic potential.

Keywords: Defect nanostructures; Ferroptosis; Membrane-camouflaged; Metal-organic framework; Multi-drug-delivery.