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Kokkoli Research GroupDepartment of Chemical Engineering and Materials Science (CEMS)

PR_b-Targeted Delivery of Tumor Necrosis Factor-α by Polymersomes for the Treatment of Prostate Cancer

Demirgöz, D., Pangburn, T.O., Davis, K.P., Lee, S., Bates, F.S., and Kokkoli, E.

Abstract

Targeted delivery of therapeutics is an active area of research with cancer being an important target because of the necessity for new and better cancer therapies. In this study we design and assess peptide functionalized polymer vesicles, or polymersomes, self assembled from poly(ethylene oxide)-b-poly(butadiene) (PEO-PBD) diblock copolymers for the treatment of prostate cancer. PR_b, a highly effective α5β1 targeting peptide that mimics the cell adhesion binding site in fibronectin, was recently developed in our group, and is here conjugated onto the surface of our polymer vesicles with controlled orientation, ensuring proper and uniform orientation of the targeting peptide at the interface. Polymer vesicles, although often proposed as highly advantageous drug delivery agents, have so far seen limited use as targeted delivery carriers with this study focusing on targeting the polymer vesicles to prostate cancer cells and delivering a therapeutic payload. PR_b-functionalized polymer vesicles are found to effectively internalize within prostate cancer cells after adhering specifically to α5β1 integrins expressed on the surface of prostate cancer cells. Internalization of polymer vesicles was found to be dependent on the surface concentration of PR_b. In addition polymer vesicles encapsulating a model protein therapeutic, tumor necrosis factor-α (TNFα), were delivered to LNCaP human prostate cancer cells in vitro. Dramatic improvements in the cytotoxic potential of the delivered TNFα were achieved for PR_b-functionalized polymer vesicles, while polymer vesicles functionalized with the peptide GRGDSP were found to perform no better than non-functionalized polymer vesicles. The potency and specificity of these PR_b-targeted polymersomes show great promise for the targeted delivery of therapeutics.

Citation
Demirgöz, D., Pangburn, T.O., Davis, K.P., Lee, S., Bates, F.S., and Kokkoli, E. "PR_b-Targeted Delivery of Tumor Necrosis Factor-α by Polymersomes for the Treatment of Prostate Cancer", Soft Matter, 2009, 5 (10): 2011 - 2019.
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