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Therapeutic peptide delivery via aptamer-displaying, disulfide-linked peptide amphiphile micelles

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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.

Graphical abstract: Therapeutic peptide delivery via aptamer-displaying, disulfide-linked peptide amphiphile micelles

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Publication details

The article was received on 31 Jul 2019, accepted on 30 Sep 2019 and first published on 07 Oct 2019


Article type: Paper
DOI: 10.1039/C9ME00092E
Mol. Syst. Des. Eng., 2019, Advance Article

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    Therapeutic peptide delivery via aptamer-displaying, disulfide-linked peptide amphiphile micelles

    J. D. Smith, L. N. Cardwell, D. Porciani, A. Nolla, B. T. Cornelison, M. C. Schulte, F. Gallazzi, D. H. Burke, M. A. Daniels and B. D. Ulery, Mol. Syst. Des. Eng., 2019, Advance Article , DOI: 10.1039/C9ME00092E

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