2. Academic Validation
  3. Bioengineered bacterial extracellular vesicles for targeted delivery of an osteoclastogenesis-inhibitory peptide to alleviate osteoporosis

Bioengineered bacterial extracellular vesicles for targeted delivery of an osteoclastogenesis-inhibitory peptide to alleviate osteoporosis

  • J Control Release. 2025 Jun 10:382:113751. doi: 10.1016/j.jconrel.2025.113751.
Xiangxiang Kong 1,  Han Liu 2,  Sumeng Chen 1,  Zhinan Liu 1,  Qin Chen 3,  Xiang Li 4,  Honggang Hu 5,  Jiacan Su 6,  Yejiao Shi 7
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China; MedEng-X Insititutes, Shanghai University, Shanghai 200444, China; School of Medicine, Shanghai University, Shanghai 200444, China.
  • 2 Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China; MedEng-X Insititutes, Shanghai University, Shanghai 200444, China; Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: [email protected].
  • 3 School of Life Sciences, Shanghai University, Shanghai 200444, China.
  • 4 School of Pharmacy, Naval Medical University, Shanghai 200433, China.
  • 5 School of Medicine, Shanghai University, Shanghai 200444, China; Shanghai Integration and Innovation Center of Marine Medical Engineering, Shanghai 200444, China. Electronic address: [email protected].
  • 6 Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China; MedEng-X Insititutes, Shanghai University, Shanghai 200444, China; Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address: [email protected].
  • 7 Institute of Translational Medicine, Shanghai University, Shanghai 200444, China; National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai 200444, China; MedEng-X Insititutes, Shanghai University, Shanghai 200444, China; Shanghai Integration and Innovation Center of Marine Medical Engineering, Shanghai 200444, China. Electronic address: [email protected].
PMID: 40268198 DOI: 10.1016/j.jconrel.2025.113751
Abstract

Osteoporosis (OP) is a systemic skeletal disease commonly found in women after 55 years old and men after 65 years old. With the worldwide aging of population, its prevalence rate is increasing rapidly, bringing huge financial burdens to all countries. As a potential alternative to the conventional OP therapeutics with limited efficacies and side effects, a linear peptide FRATtide capable of binding with phosphorylated GSK3β has been discovered by us to inhibit osteoclastogenesis thus reduce bone loss. While its poor proteolytic stability and osteoclast targetability hinder its effective in vivo treatment. As such, Bacterial extracellular vesicles secreted by the rationally recombinant probiotics Escherichia coli Nissle 1917 that express pre-osteoclast fusion protein DC-STAMP (BEV-DCS) are engineered and exploited as delivery vehicles. The BEV-DCS not only protect FRAT from enzymatic degradation but also enable its targeted intracellular delivery into pre-osteoclasts. On the ovariectomy mouse model, the FRAT encapsulated BEV-DCS (FRAT@BEV-DCS) exhibit remarkable bone targeting capacity and osteoporosis ameliorating efficacy without any obvious toxicity. These results reveal the great potential of FRAT@BEV-DCS as a novel therapeutic option for the effective and safe OP treatment.

Keywords

Bacterial extracellular vesicle; Bone targeting; Intracellular delivery; Osteoporosis; Stability.

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