Rational engineering of ferritin nanocages for targeted therapy of osteoarthritis

Yi He; En Ren; Zhenhui Lu; Haimin Chen; Zainen Qin; Junqing Wang; Mingwei He; Gang Liu; Li Zheng; Jinmin Zhao

doi:10.1016/j.nano.2020.102210

Rational engineering of ferritin nanocages for targeted therapy of osteoarthritis

Nanomedicine. 2020 Aug:28:102210. doi: 10.1016/j.nano.2020.102210. Epub 2020 Apr 23.

Authors

Yi He¹, En Ren², Zhenhui Lu¹, Haimin Chen³, Zainen Qin³, Junqing Wang², Mingwei He⁴, Gang Liu⁵, Li Zheng⁶, Jinmin Zhao⁷

Affiliations

¹ Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China.
² State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
³ Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
⁴ Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Department of Orthopaedis Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China.
⁵ Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China. Electronic address: gangliu.cmitm@xmu.edu.cn.
⁶ Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China. Electronic address: zhengli224@163.com.
⁷ Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Guangxi Collaborative Innovation Center for Biomedicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China; Department of Orthopaedis Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, 530021, China. Electronic address: zhaojinmin@126.com.

PMID: 32334102
DOI: 10.1016/j.nano.2020.102210

Abstract

Intra-articular (IA) drug delivery to treat osteoarthritis (OA) is limited by the short retention time of drugs in the joints due to poor specific targeting and non-responsiveness under acidic environment. A cartilage-targeting peptide was engineered to the surface of ferritin nanocages (CT-Fn) and loaded with an anti-inflammatory drug, metformin (Met), via the self-assembling nature of Fn nanocages. It demonstrated that the CT-Fn/Met could specifically bind to type II collagen, leading to the downregulation of catabolic markers of OA and promotion of cartilage-specific makers in IL-1β-induced chondrocytes. IA delivery of CT-Fn/Met prolonged the retention time for 3 weeks and remarkably reduced inflammation. Moreover, better release under acidic conditions which enabling longer retention time of Met after IA delivery in OA joints for one more week. CT-Fn/Met could target and efficiently enter chondrocytes, further inducing prolonged IA accumulation and achieving enhanced therapeutic efficacy for OA treatment.

Keywords: Drug delivery; Ferritin; Metformin; Nanocages; Osteoarthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Inflammatory Agents / therapeutic use*
Cell Survival / drug effects
Collagen Type II / metabolism
Drug Delivery Systems / methods*
Ferritins / chemistry*
Fluorescent Antibody Technique
Immunohistochemistry
Male
Metformin / therapeutic use
Mice
Mice, Inbred C57BL
Osteoarthritis / drug therapy*
Real-Time Polymerase Chain Reaction

Substances

Anti-Inflammatory Agents
Collagen Type II
Ferritins
Metformin