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

Molecular Systems Design & Engineering Pub Date: 2019-10-07 DOI: 10.1039/C9ME00092E

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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