Title
Therapeutic peptide delivery via aptamer-displaying, disulfide-linked peptide amphiphile micelles
Author
Josiah D. Smith, Leah N. Cardwell, David Porciani, Andrea Nolla, Brenna T. Cornelison, Megan C. Schulte, Fabio Gallazzi, Donald H. Burke, Mark A. Daniels, Bret D. Ulery
Year
2019
Journal
Molecular Systems Design & Engineering
Abstract
Peptide amphiphile micelles (PAMs) are a powerful platform technology for improving the delivery of therapeutic and prophylactic peptides. While previous research has shown aptamer-displaying PAMs enhance cell association, transportation to intracellular targets still remains a substantial hurdle for these biomaterials. In this article, we detail our efforts to address this challenge through the creation of disulfide-linked peptide amphiphile (PAs). These molecules were found to self-assemble in water into PAMs for which lipidated DNA oligomers (i.e., antitail amphiphiles – AAs) could be entrapped and used to tether aptamers (Apt) to the nanoparticle surface. These Apt∼A/PAMs were physically characterized and evaluated for their blood-serum stability using fetal bovine serum exposure and glutathione reduction. To assess their enhanced intracellular delivery capacity and therapeutic functionality, PAMs bearing cell-penetrating peptide modified “Plenty of SH3 domains” scaffold protein competitive inhibitor (Tat-POSH) and B cell lymphoma targeting aptamer (C10.36) were incubated with Ramos cells, a non-Hodgkin lymphoma cell line. C10.36∼A/PAMs were found not only to be stable in blood-like conditions, but also to be capable of facilitating delivery of therapeutic Tat-POSH peptide to Ramos cells in vitro.
Instrument
J-815
Keywords
Circular dichroism, Secondary structure, Chemical stability, Biochemistry