Shape‐Dependent Targeting of Injured Blood Vessels by Peptide Amphiphile Supramolecular Nanostructures

Abstract

Targeting of vascular intervention by systemically delivered supramolecular nanofibers after balloon angioplasty is described. Tracking of self-assembling peptide amphiphiles using fluorescence shows selective binding to the site of vascular intervention. Cylindrical nanostructures are observed to target the site of arterial injury, while spherical nanostructures with an equivalent diameter display no binding.

Self-assembling peptide-based building blocks in medical applications

“…Novel methods of diagnosing atherosclerotic plaques are particularly needed because of their asymptomatic yet deadly nature; while current clinical imaging options are limited in their ability to detect rupture instability, cardiovascular diseases remain to be the single leading cause of deaths globally [152]. In an effort to provide a novel molecular imaging tool, fluorescently-labeled spherical PAs have also incorporated targeting peptides to monocytes [149], endothelial cells [153], and collagen [154] to detect vulnerable, diseased, and injured blood vessels. Additional studies conducted in large animals will be the next step to determine the potential of PAs as a potential molecular imaging tool for the clinic.…”

Gasotransmitter delivery via self-assembling peptides: Treating diseases with natural signaling gases

“…Although there exists a recent report on systemically delivered nanomaterials that target an injured blood vessel through the bloodstream [145], localized delivery directly to the injured artery after surgery is the more common strategy. To address this problem, Stupp and Kibbe used the PA palmitate-AAAAGGGLRKKLGKA (palmitate = CH 3 (CH 2 ) 14 C(O)-), which contains the heparin binding sequence LRKKLGKA [197].…”

Targeting collagen for diagnostic imaging and therapeutic delivery

“…This peptide was attached to lipid-polymeric nanoparticles to target sites of balloon angioplasty [27]. It was also incorporated into a peptide amphiphile sequence in order to target areas of vascular intervention [28]. When conjugated to a β-sheet forming domain, self-assembled nanofibers were formed, which were shown to bind to exposed collagens on the injured blood vessels for up to two days.…”

“…Langer and coworkers reported micelle-based paclitaxel delivery system that display HWGSLRA on micelle surface as “hooks” for binding to collagen (Figure 2C) [27]. Also, peptide amphiphiles can self-assemble into nanofibers (Figure 2D, top) or nanospheres (Figure 2D, bottom) which disiplay high density of collagen binding peptides on their surfaces [28]. It was shown that nanofibers have preferential binding to injured vessels and are cleared at a slower rate relative to nanospheres of similar dimensions.…”