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October 27, 2023
Pharmaceutical Sciences Seminar Series
Peptides Materials from Self-Assembly and Their Use In Therapy
(Drug DELIVERY Specific Seminar)
- Joel Schneider, PhD
- National Cancer Institute, NIH
Peptides have proven useful as building blocks for the construction of materials. It is now well-known that naturally derived or de novo designed peptides can assemble into a myriad of morphologies including membranes, nano- and microscopic spheres, tubes, ribbons, tapes, flowers, and even teeth. However, the most ubiquitous shape is most likely the fibril. Fibrils are privileged morphologies in that they are capable of higher order assembly forming fibral networks that constitute the formation of hydrogel materials. The physical, mechanical and biological properties of peptide gels can be tuned through design at the molecular level to enable a wide range of therapeutic applications. Understanding the assembly mechanisms by which these materials are formed and the ultimate structures they form to molecular detail catalyze their development towards targeted biomedical applications. [1] We designed a class of peptide hydrogels that allows for the direct encapsulation of therapeutics and their subsequent local delivery to tissue. Peptide assembly leading to gels can be triggered in the presence of small molecules, proteins, nucleic acids, cells, and nanoparticles resulting in their direct encapsulation. Resulting gels display shear-thin/recovery mechanical properties, allowing their direct application to targeted tissue by syringe or spray, where they deliver their payload locally. Through the design of over 200 sequences, we have developed a deep mechanistic and structural understanding of our materials. This has allowed the development of gels that facilitate a broad range of applications including microanastomosis [2], gels that limit tissue rejection after organ and vascularized composite allotransplantation [3], gel antibacterial coatings for medical implants [4], and gels as treatments for mesothelioma [5], a hard-to-treat cancer.
[1] Tania L. Lopez-Silva and Joel P. Schneider (2021) Curr. Opin. Chem. Biol., 64, 131.
[2] Daniel J. Smith, Gabriel A. Brat, et al. (2016) Nature Nanotechnology, 11, 95.
[3] Poulami Majumbder, Yichuan Zhang, et al. (2020) Small, 16, 2002791.
[4] Galit Fichman, Caroline Andrews, et al. (2021) Adv. Materials, 16, 2103677.
[5] Poulami Majumbder, Anand Singh, et al. (2021) Nature Nanotechnology, 16, 1251
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