The Effect of Amino Acid Configuration on the Biodistribution of Peptide Nanofiber / 天津医药

ABSTRACT

Objective To compare the biodistribution difference of peptide nanofibers, which were self-assembled by peptide composed of L-or D-amino acids, respectively, and provide the guidance for the in vivo applications of peptide nanofibers. Methods The Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide, F and Y were D-configura-tion) were synthesized with solid phase peptide synthesis (SPPS). The structure of the two peptides was identified by nuclear magnetic resonance spectroscopy (1H NMR) and high-resolution mass spectrometry (HR-MS). The two peptides could self-assemble into nanofibers during the cooling process after being boiled. The morphology of the nanofibers was observed with transmission electron microscope (TEM). The peptides were radiolabeled with iodine-125 and self-assembled into nanofi-bers, which were then administered into BALB/c mice via tail vein. The blood samples were collected and then mice were sacrificed at 1, 3, 6 and 12 hours. The main organs (heart, liver, spleen, lung, kidney, stomach, large intestine, small intes-tine, muscle and brain) were isolated and weighed. The radioactivity of organs was detected with a gamma counter. Results The two peptides could self-assemble into nanofibers with diameter of 10-20 nanometers. There were no significant differ-ences in the diameter and morphology between two naofibers. There was significant difference in the biodistribution between two nanofibers. The blood concentration of D-fiber was (8.17±0.32)%ID/g at one hour after injection and then cleared rapid-ly from the blood. The blood concentration of L-fiber was (5.96±0.30)%ID/g at one hour after injection and maintained at a stable level for six hours. The L-fiber was mainly distributed in stomach while the D-fiber was mainly accumulated in liver. Conclusion The configuration of amino acids (D/L) could affect the biodistribution of peptide nanofibers dramatically, which may provide the guidance for the medical applications of peptide nanofibers.