Peptide fragments of human serum albumin as novel renal targeting carriers.

To develop the proper renal targeting carrier for clinical therapy, human serum albumin, as starting material, was firstly cleaved into albumin fragments and Superdex 75 and CM-Sepharose FF were used to separate and purify the degradation products. Consequently, three peptide fragments (PFs) with certain sequence named PF-A1-123, PF-A124-298 and PF-A299-585 were obtained as candidates of renal targeting carrier. Then, cytotoxicity and cellular uptake of three PFs was studied preliminarily. The results showed that three PFs had no adverse effects on the HeLa and MDCK cell even up to 5.00mg/mL and PF-A299-585 exhibited highest affinity to MDCK cells. After that, we found that PFs selectively accumulated in the kidneys, especially in the renal tubules after intravenous injection in mice by optical imaging study. Finally, Tissues distribution in vivo was utilized to verify the renal targeting profiles of PFs. Three PFs exhibited renal accumulation characteristics. In particular, about 40% injected doses of PF-A299-585 were specifically distributed into kidneys for 1h. The mean area under the curve (AUC) of PF-A299-585 in kidneys increased 13 times compared with those of PF-A1-123 and PF-A124-298. Therefore, PFs can be applied as prospective carriers for renal targeting and PF-A299-585 may be the optimal carrier.