Expression and Functional Characterization of Tumor-Targeted Fusion Protein Composed of NGR Peptide and 15-kDa Actin Fragment

Abstract

To induce tumor cell apoptosis, a modified 15 kDa actin linked with a peptide NGR "homing" into tumor or tumor vessels was expressed in Escherichia coli. After refolding and purification, this fusion protein NGR-15actin was labeled with FITC to testify whether NGR-15actin could integrate into the cytoskeleton. It was found that this targeted peptide could induce HepG2 and HeLa cells apoptosis through its effect on the cytoskeleton function by binding to cytoskeleton protein. Thus, targeted NGR-15actin could be a candidate molecule for the therapy of cancer.

The Use of Therapeutic Peptides to Target and to Kill Cancer Cells

“…This sequence homed specifically to solid tumors and, more strictly, to the endothelium of angiogenic blood vessels, and delivered a liposomal doxorubicin compound to treat orthotopic neuroblastoma xenografts in mice [111, 112]. The NGR peptide fused with a 15kDa actin fragment induced apoptosis in vitro by integrating into the cytoskeleton [113]. NGR and/or STR-R4 peptides, attached to the distal ends of PEG on liposomes, enhanced the uptake of the liposomes in CD13 positive cells [114].…”

Peptide-Conjugated Nano Delivery Systems for Therapy and Diagnosis of Cancer

“…Aminopeptidase N (or CD13) is associated with the growth of various cancers and suggested as a potential target for anti-cancer treatment. Interestingly, tripeptide Asn-Gly-Arg (NGR) is a ligand of aminopeptidase N (APN/CD13), which is found to be overexpressed in cancer cells and also target neoangiogenic blood vessels [118]. APNtargeted NDS have been developed by various groups; for example, after the intravenous injection of the c-Myc siRNA loaded in NGR-modified PEGylated liposomes, they are delivered efficiently to the HT1080 fibrosarcoma cytoplasm.…”