Integrin αvβ3 targeting activity study of different retro-inverso sequences of RGD and their potentiality in the designing of tumor targeting peptides

Retro-inverso peptide represented the isomer of a parent peptide in which the direction of the sequence was reversed and the chirality of each amino acid residue was inverted. Generally, retro-inverso peptides possessed equal or even higher activities compared to the original peptide. RGD was a commonly used ligand for tumor and vascular targeting due to its affinity to integrin alpha(v)beta(3) receptors. The biological activity study of the isomers of RGD would indeed provide useful suggestions for the design of tumor targeting peptides. Therefore, the tumor targeting activities of octa-arginine which was modified with different retro-inverso sequences of RGD peptide were investigated in this study. Three different tandem peptides (R8-GDGR, R8-GdGr and R8-GdGR) were designed on the basis of R8-GRGD. The tumor targeting activities of these tandem peptides were evaluated both in vitro and in vivo. Finally, R8-GdGR displayed selective binding affinity to integrin alpha(v)beta(3) at the cellular level, and exhibited efficient tumor homing and penetrating capabilities in vivo. Meanwhile, R8-GdGR also showed stronger neovessel targeting ability compared to the others. In conclusion, all the results demonstrated that dGR possessed similar biological activity to RGD and was a potential ligand for further designing of tumor targeting peptides.