Molecular Changes in the Vasculature of Injured Tissues

Abstract

We have explored molecular specialization of the vasculature of regenerating wound tissue in the skin and tendons to identify a different repertoire of markers from that obtained by studying tumor vasculature. We screened a phage-displayed peptide library for peptides that home to wounds in mice and identified two peptides that selectively target phage to skin and tendon wounds: CARSKNKDC (CAR) and CRKDKC (CRK). CAR is homologous to heparin-binding sites in various proteins and binds to cell surface heparan sulfate and heparin. CRK is similar to a segment in thrombospondin type 1 repeat. Intravenously injected CAR and CRK phage, as well as fluorescein-labeled CAR and CRK peptides, selectively accumulated at wound sites, where they partially co-localized with blood vessels. The CAR peptide showed a preference for early stages of wound healing, whereas the CRK favored wounds at later stages of healing. The CAR peptide was internalized into the target cells and delivered the fluorescent label into the cell nuclei. These results identify new molecular markers in wound tissues and show that the expression of these markers in wound vasculature changes as healing progresses. The peptides recognizing these markers may be useful in delivering treatments into regenerating tissues.

Nanoparticle-induced vascular blockade in human prostate cancer

“…This is attributable in part to the selective accumulation of CREKA-NWs, and the nanoworm mixture, in tumor vessels. Both the peptide and the iron oxide component of the nanoparticles are responsible for the thrombotic activity, because other types of nanoparticles coated with CREKA and the free CREKA peptide lack this activity, 26,32 and iron oxide nanoworms coated with tumor-homing peptides other than CREKA (CRKDKC and CGKRK) also do not cause clotting. Iron oxide nanoparticles are known to be procoagulants, and the affinity of CREKA for clotting products apparently enhances that activity.…”

“…Tumor volume was calculated by the following formula: volume ϭ (d 2 ϫ D)/2, where d is the smallest and D the largest tumor diameter. 26 …”

C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration

“…The CPPs are not selective; they are taken up into nearly all types of cells. Internalizing peptides that are tissue specific have also been described (6)(7)(8)(9). CPP derivatives with cationic and anionic modules linked by a protease-sensitive linker have been developed for tumor-selective delivery (10).…”

Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice

“…Here we have investigated whether adding a wound-targeting function to decorin would enhance its activity. We recently used in vivo phage display to identify peptides that home to angiogenic blood vessels in regenerating tissues (19). Phage expressing the most potent wound-homing peptide obtained, CARSKNKDC (CAR) homed up to 200-fold more than control phage to blood vessels in regenerating skin, skeletal muscle, and tendons.…”