Optimized biotinylation-based loading of therapeutic peptides/proteins into nanoscale extracellular vesicles for targeted cancer therapy

Researchers from Kyoto University have developed a novel method to significantly improve how therapeutic peptides and proteins are loaded into extracellular vesicles (EVs), tiny natural packages released by cells. These nanoscale vesicles have shown great promise as delivery vehicles that can transport drugs directly to target cells, making treatments more precise and effective.

In their approach, the team used fusion proteins combined with a special biotinylation reaction originally from a microorganism called Sulfolobus tokodaii. This allowed multiple therapeutic molecules to attach to a single carrier protein, dramatically increasing the amount of cargo loaded into large extracellular vesicles. Using this method, EVs carrying inhibitors that block important signaling proteins involved in cancer progression, such as protein kinase A (PKA) and STAT3, were prepared.

These loaded EVs successfully influenced tumor-associated macrophages (immune cells in the tumor environment), changing their behavior in ways that helped suppress tumor growth. In mouse models of breast cancer, EVs loaded with PKA inhibitors boosted the effectiveness of anti-PD-1 antibody therapy, a key immunotherapy approach. This work shows that improving the loading of therapeutic peptides and proteins into EVs can unlock their full potential as targeted cancer treatments.