Engineered mesenchymal stem cell-derived extracellular vesicles constitute a versatile platform for targeted drug...

Area of Science:

• Biotechnology
• Nanomedicine
• Regenerative Medicine

Background:

• Extracellular vesicles (EVs) are biocompatible therapeutic carriers but lack specific targeting capabilities, hindering clinical use.
• Genetic engineering of EVs can overcome limitations in targeted drug delivery for various diseases.

Purpose of the Study:

• To develop a versatile platform for targeted drug delivery using engineered extracellular vesicles.
• To demonstrate the efficacy of streptavidin-modified BMSC-EVs in preclinical models of cancer and arthritis.

Main Methods:

• Genetically engineered bone marrow mesenchymal stem cells (BMSCs) to overexpress streptavidin (SA) on their EVs (BMSC-EVs).
• Confirmed SA expression on BMSC-EVs using biotin-coated gold nanoparticles.
• Modified BMSC-EVs with targeting ligands (pH-sensitive peptide, anti-EGFR, anti-HER2, anti-IL12/IL23) for specific delivery in cancer and arthritis models.

Main Results:

• SA-overexpressing BMSC-EVs demonstrated targeted drug delivery in hypoxic tumors and specific targeting of EGFR+ and HER2+ breast cancers.
• Modified BMSC-EVs effectively accumulated in arthritic joints and reduced inflammation in a collagen-induced arthritis model.
• SA-overexpressing BMSC-EVs exhibited low immunogenicity and high in vivo safety.

Conclusions:

• Streptavidin-engineered BMSC-EVs provide a versatile platform for targeted drug delivery across diverse therapeutic applications.
• The ability to functionalize BMSC-EVs with various biotinylated molecules allows for tailored targeting strategies.
• Engineered BMSC-EVs represent a promising and safe drug delivery vehicle for clinical translation.