Tumour-homing peptides: tools for targeting, imaging and destruction

Abstract

Each normal organ and pathological condition contains organ- or disease-specific molecular tags on its vasculature that constitute a vascular 'zip code' system. Tissue-selective tumour metastasis may also depend on vascular addresses. We have used phage display peptide libraries to map disease-specific differences in the vasculature. By using this technology, we have isolated several peptides which are targeted specifically to tumour blood vessels, lymphatic vessels and/or tumour cells. Some of the tumour-homing peptides recognize common angiogenesis markers and are capable of binding to several types of tumour, whereas other peptides recognize tumour-type-specific differences. We have also shown that the vasculature of a pre-malignant lesion differs from that of a full-blown tumour and also from the vasculature of the corresponding normal organ. Our peptides have revealed molecules that act as novel biomarkers of this vascular heterogeneity. Interestingly, some of our homing peptides are able to penetrate the target cells. This internalization differs from that of the Tat, penetratins and other related peptides in that our peptides enter the cell in a cell-type-specific manner. These peptides appear to be able to concentrate in the target tissue, making them particularly efficient delivery vectors for the targeting of drugs, other therapeutic moieties and imaging agents.

Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells

“…The development of peptide-based therapeutics has had promising results (Thayer, 2011), both in terms of efficacy and targeting specificity (Aina et al, 2002;Enbäck and Laakkonen, 2007;Vlieghe et al, 2010). Biodegradable polyester matrices, in particular, feature in many innovative approaches evaluated over the past four decades.…”

Noncationic Peptides Obtained From Azurin Preferentially Enter Cancer Cells

“…Small arginine-rich and other cationic peptides generated from phage-displayed peptide libraries, initially characterized by the RGD (Arg-Gly-Asp) sequence that recognizes the integrin family of cell surface receptors important to the invasion of tumor cells (8), are also potential carriers for imaging (9) and therapeutic agents. These peptides enter cells in an energydependent manner (9) and can distinguish between normal and malignant vasculature (10,11) and lymphatic tissue in murine systems (9). The latter also induce apoptosis in tumor types, which also bind the peptide (9).…”

Photoacoustic molecular imaging with functional nanoparticles

“…82 As an alternative to molecular targeting ligands, peptides display high binding a±nity and several advantages such as convenient synthesis and chemical modi¯cation, good tissue penetration, low immunogenicity, favorable pharmacokinetics and acceptable in vivo stability and integrity. 65,66 In this review, we enumerate iterative phage display selection to identify two novel high a±nity binding oligopeptides selective and speci¯c for UMR-106 cell. Then, the identi¯ed oligopeptides PT6 (PPTHPPP) and PT7 (PPSHTPT) were, respectively, conjugated to GNRs to develop speci¯c nanoprobes for PAI of OS shown in Fig.…”