Sliding Bioactive Peptides for Therapeutic Delivery

NU 2023-142

INVENTORS

Samuel I. Stupp*
Federico Lancia
Madison E. Strong
Matias A. Alvarez-Saavedra

SHORT DESCRIPTION

This technology involves the design and engineering of peptide amphiphile nanofibers that deliver bioactive peptides both extra- and intra-cellularly. The bioactive peptides can slide along these structures to enhance their mobility and bioactivity.

BACKGROUND

Neurotrophic factor proteins and peptide mimetics, commonly used in regenerative therapies, often suffer from rapid degradation. Peptide amphiphiles (PA) nanofibers have been designed to improve stability and efficacy by coassembling mimetic peptide sequences onto a backbone, but these structures are less dynamic and limit the accessibility of the bioactive peptide to cell receptors. More dynamic designs can sacrifice nanofiber stability, resulting in inefficient micelles. Additionally, previous PA designs lack control over extra- or intra-cellular delivery, limiting the scope of their application in conditions that require distinct modes of action.

ABSTRACT

Northwestern researchers have developed dynamic peptide amphiphiles (PA) that display peptides capable of sliding freely along nanofibers. This invention enhances the accessibility of the bioactive sequence while maintaining the nanofiber structural integrity. Using a ciliary neurotrophic factor (CNTF) mimetic sequence, this dynamic design demonstrates superior bioactivity, including enhanced phagocytosis in microglia and neurite outgrowth. The tunable “sliding” sequences allows for both extra- and intra-cellular delivery, with the flexibility to swap sequences for different targets. Additionally, the PA backbone protects the bioactive slider from enzymatic degradation, offering a more cost-effective alternative to soluble peptides or proteins.

APPLICATIONS