Graduate Student Katrina Brandmier

"Outer Membrane Vesicles as a Vehicle for Transdermal Drug Delivery"

Melanoma is an aggressive type of skin cancer with high rates of relapse, rapid progression, and metastasis. Current cancer therapies for melanoma are limited due to high toxicity and limited specificity. Recently, outer membrane vesicles (OMVs) have been of particular interest as a vehicle for transdermal drug delivery. Transdermal drug delivery (TDD) is favored clinically due to its ability to overcome uncontrolled delivery and be administered autonomously1,2. The current difficulty with TDD is the skin stratum corneum acts as a barrier that will not allow the majority of biomacromolecules to pass through into the skin, making it difficult for drugs to penetrate the skin. However, recent studies have discovered that OMVs derived from bacteria cells may be able to penetrate through the stratum corneum, making transdermal drug delivery a promising approach.

Throughout my seminar, I will discuss research that has shown how OMVs can be used as a vehicle for transdermal drug delivery. In one study, researchers engineered transformed Escherichia coli (E. coli) derived outer membrane vesicles (named TEVs) and modified them by integrin αvβ3 targeting peptide1. αvβ3 is the vitronectin receptor, a protein found in human serum that plays important roles in cell signaling3. The αvβ3 integrin binds specifically well to peptides with an Arg-Gly-Asp (RGD) triple-peptide motif3. The high specificity and binding efficiency of the integrin with the tumor necrosis factor-apoptosis inducing ligand (TRAIL), allows promising drug delivery using OMVs as the vehicle of transport4. In another study, researchers investigate whether the combinational use of near-infrared light and TRAIL as a phototreatment can cause sensitization in resistant tumor cells2. The combination of these studies represents a promising new treatment for melanoma, as well as platform for modification of OMVs to treat various diseases.

(1) Gu, T.-W.; Wang, M.-Z.; Niu, J.; Chu, Y.; Guo, K.-R.; Peng, L.-H. Outer Membrane Vesicles Derived from E. Coli as Novel Vehicles for Transdermal and Tumor Targeting Delivery. Nanoscale 2020, 12 (36), 18965–18977. https://doi.org/10.1039/d0nr03698f.
(2) Peng, L.-H.; Wang, M.-Z.; Zhang, L.; Niu, J.; Shao, H.-T.; Yuan, T.-J.; Jiang, Z.-H.; Gao, J.-Q.; Ningt, X.-H. Engineering bacterial outer membrane vesicles as transdermal nanoplatforms for photo-TRAIL–programmed therapy against melanoma. Science Advances 2020, 6(27), https://www.science.org/doi/10.1126/sciadv.aba2735#F1 .
(3) Integrin αvβ3-Targeted Cancer Therapy https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901818/.
(4) Dai, X.; Zhang, J.; Arfuso, F.; Chinnathambi, A.; Zayed, M.; Alharbi, S. A.; Kumar, A. P.; Ahn, K. S.; Sethi, G. Targeting TNF-Related Apoptosis-Inducing Ligand (TRAIL) Receptor by Natural Products as a Potential Therapeutic Approach for Cancer Therapy. Exp Biol Med (Maywood) 2015, 240 (6), 760–773. https://doi.org/10.1177/1535370215579167.