Personalized medicine with functionalized extracellular vesicles

Personalized medicine is an innovative approach transforming modern oncology, aiming to tailor treatments to individual patients based on their unique genetic and molecular profiles. A promising advancement in this field involves using extracellular vesicles (EVs) derived from lung cancer cells. These tiny particles, naturally released by cells, can be engineered to deliver therapeutic drugs directly to cancer cells, potentially enhancing treatment effectiveness while minimizing side effects.

The Role of Extracellular Vesicles in Cancer Therapy

Extracellular vesicles are small, membrane-bound particles that facilitate communication between cells by transporting molecules such as proteins and RNA. In cancer therapy, EVs can be modified to carry therapeutic agents directly to tumor cells, offering a targeted treatment approach. However, a significant challenge in using EVs for cancer therapy is ensuring they specifically target cancer cells without affecting healthy cells.

Enhancing EV Targeting with Heptapeptides

To address this challenge, researchers at the University of Warsaw have developed a method to functionalize the surface of EVs with specific ligands, which are molecules that bind to target cells with high specificity. In this study, the researchers used a heptapeptide—a short chain of seven amino acids—with a strong affinity for lung cancer cells. The heptapeptide sequence, PTHTRWA, was identified as the most effective in binding to lung cancer cells.

The heptapeptide was attached to the EV membrane either through its C-terminal or N-terminal end, essentially acting as a targeting mechanism to direct the EVs to lung cancer cells.

Testing the Functionalized EVs

To verify the effectiveness of these functionalized EVs, several experiments were conducted:

  1. Lipid Membrane Models: The researchers used models that mimic normal and cancerous cell membranes to observe how well the PTHTRWA-functionalized EVs bind to cancer cells compared to normal cells.
  2. Cell Culture Studies: Human lung cancer cells (A549) and normal bronchial epithelial cells (BEAS-2B) were exposed to the functionalized EVs. The results showed that the EVs effectively targeted and bound to the cancer cells while sparing the normal cells.
  3. Animal Studies: In a more advanced test, the researchers injected these engineered EVs, loaded with superparamagnetic iron oxide nanoparticles (SPIO), into mice with lung cancer. Magnetic resonance imaging (MRI) revealed that the functionalized EVs successfully reached and accumulated in the tumor, demonstrating their potential for targeted drug delivery.
  4. Molecular Dynamics Studies: Using computer simulations, the researchers confirmed that the PTHTRWA peptide has a high affinity for the α5β1 integrin, a protein often overexpressed on the surface of cancer cells. This binding specificity is crucial for the targeted action of the functionalized EVs.

Safety and Efficacy

Ensuring that these engineered EVs are safe for use is as important as proving their effectiveness. Preclinical safety assays showed no cytotoxic (cell-damaging) or genotoxic (DNA-damaging) effects from the PTHTRWA-functionalized EVs. This finding is promising, indicating that these EVs can potentially be used in human patients without harmful side effects.

Conclusion

This study represents a significant step forward in personalized cancer therapy. By functionalizing EVs with specific peptides, these researchers have developed a targeted delivery system that can precisely direct therapeutic agents to lung cancer cells. This approach not only enhances the effectiveness of the treatment but also reduces the risk of damaging healthy cells.

As personalized medicine continues to evolve, such innovations hold the promise of more effective and safer cancer treatments, offering hope to patients worldwide. The successful use of functionalized EVs in targeting lung cancer cells could pave the way for similar strategies in treating other types of cancer, marking a new era in oncology.

Kowalczyk A, Dziubak D, Kasprzak A, Sobczak K, Ruzycka-Ayoush M, Bamburowicz-Klimkowska M, Sęk S, Rios-Mondragon I, Żołek T, Runden-Pran E, Shaposhnikov S, Cimpan MR, Dusinska M, Grudzinski IP, Nowicka AM. (2024) Surface-Bioengineered Extracellular Vesicles Seeking Molecular Biotargets in Lung Cancer Cells. ACS Appl Mater Interfaces [Epub ahead of print]. [article]

Leave a Reply

Your email address will not be published. Required fields are marked *

*