Abstract
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.
Highlights
Ovarian cancer is the seventh leading cancer diagnosis and eighth leading cause of cancer mortality among women [1]
Peptide, these related 14-mer peptides exhibited affinity for Fe3 O4 -MNPs. Both QL-TYand QL-YT-modified Fe3 O4 -MNPs nonspecifically bonded to A2780 cells, HUVECs, and L929 cells, but LQ-YT-modified Fe3 O4 -MNPs bonded to A2780 tumor cells
In various combinations of Q-L and T-Y 7-mer peptides, the 14-mer peptide LQ-YT was connected in the CN-NC terminal connection configuration, while QL-YT, QL-TY, and LQ-TY peptides were in the NC-NC, NC-CN, and CN-CN configurations, respectively
Summary
Ovarian cancer is the seventh leading cancer diagnosis and eighth leading cause of cancer mortality among women [1]. It is the most lethal gynecologic malignancy [2] and has become still more known for its marked tissue heterogeneity [3]. While chemotherapy and cytoreductive surgery have exhibited favorable curative outcomes for early-stage ovarian cancer, more than 75% of cases advance to stage III or IV. The lack of effective means for early diagnoses and the deficiency of specific targeting in chemotherapy have been regarded as the main barriers to improving treatment response and cure rates for ovarian cancer patients [5,6].
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