Cyclic and dimeric fibroblast growth factor 2 variants with high biomedical potential

Area of Science:

• Biochemistry
• Molecular Biology
• Regenerative Medicine

Background:

• Fibroblast Growth Factor 2 (FGF2) regulates critical cellular processes but has limited medical application due to poor stability and broad activity.
• Current FGF2 applications include basic research, cell culture, regenerative medicine, and anticancer drug delivery.

Purpose of the Study:

• To engineer novel FGF2-based macromolecules with improved stability and tailored biological activities.
• To investigate the impact of FGF2 macromolecular architecture on adipocyte glucose uptake.
• To develop FGF2 variants for targeted cancer therapy.

Main Methods:

• Sortase A-mediated cyclization and oligomerization were employed to create FGF2 variants.
• Heparin-switchable FGF2 variants were generated and characterized.
• The efficacy of engineered FGF2 in stimulating cell proliferation, migration, and glucose uptake was assessed.
• Hyper-stable FGF2 variants were utilized to construct drug carriers for cancer cell targeting.

Main Results:

• Heparin-switchable FGF2 variants exhibited enhanced stability and improved stimulation of cell proliferation and migration.
• Adipocyte glucose uptake was modulated by the specific architecture of FGF2 oligomers.
• Engineered FGF2-based drug carriers effectively targeted and killed FGFR1-overexpressing cancer cells.

Conclusions:

• FGF2 engineering via sortase A-mediated cyclization and oligomerization yields stable variants with enhanced functionality.
• These engineered FGF2 macromolecules hold significant promise for applications in regenerative medicine and precise anti-cancer therapies.
• The study provides a strategic framework for designing growth factor variants for advanced medical applications.