Novel Bi-Functional 14-mer Peptides with Both Ovarian Carcinoma Cells Targeting and Magnetic Fe₃O₄Nanoparticles...

Fe₃O₄ magnetic nanoparticles (Fe₃O₄-MNPs) have attracted much interest for their potential medical applications due to their desirable magnetic properties. However, their potential cytotoxicity, high RES clearance in circulation, and nonspecific distribution in tissue might be the main obstacles in practice. In the present study, a novel bi-functional 14-mer peptide with both ovarian carcinoma cells targeting and magnetic Fe₃O₄ nanoparticles affinity was designed and synthesized, and then a facile and effective modification method was developed to bestow the Fe₃O₄-MNPs with tumor-targeting capability via modification, using the bi-functional peptides. First, on the basis of a tumor-targeting 7-mer peptide QQTNWSL (Q-L) and another Fe₃O₄-MNPs-targeting 7-mer peptide TVNFKLY (T-Y)-screened by phage-displayed peptide libraries-two bi-functional 14-mer peptides sequenced as LSWNTQQ-YLKFNVT (abbreviated as LQ-YT) and QQTNWSL-YLKFNVT (QL-YT) were synthesized through combining the Q-L peptide and T-Y peptide in predetermined configurations. Their specificity for bonding with A2780 tumor cells and affinity for Fe₃O₄-MNPs were verified. Then the bi-functional 14-mer peptides were applied to modify the Fe₃O₄-MNPs. Results showed that both bi-functional 14-mer peptides could be conjugated to the Fe₃O₄-MNPs surface with high affinity. Immunofluorescence and Prussian blue staining assays indicated that the LQ-YT-modified Fe₃O₄-MNPs could specifically bond to A2780 tumor cells. In addition to our findings suggesting that more β-turns and random coils are conducive to increasing polypeptide surface area for binding and exposing the target group and bonding sites on LQ-YT to external targets, we demonstrated that the bi-functional 14-mer peptide has affinity for Fe₃O₄-MNPs, and that Fe₃O₄-MNPs, which was modified with a 14-mer peptide, could be bestowed with a targeting affinity for ovarian carcinoma cells.