De Novo Computational Design for Development of a Peptide Ligand Oriented to VEGFR-3 with High Affinity and Long Circulation

Molecular Pharmaceutics
Hong M LiYue Wang

Abstract

The overexpression of VEGFR-3 is correlated with a worse prognosis in lung cancer and has been regarded as a rational target for specific drug delivery. Here, VEGFR-3 homing peptide library was efficiently established by computational design. Strong fluorescent signals of selected peptides were observed in A549 cells, but much weaker in other cells. The positive immunostaining overlapped with VEGFR-3 confirmed high affinity and selectivity of one novel peptide (CP-7). In addition, cell uptake of FITC-CP-7 peptide was significantly blocked by coinjection of excess CP-7 peptide. After labeled with 131I, the profile of pharmacology and biodistribution could be traced in vivo. The 131I-radiolabeled CP-7 peptide conjugates were >85% stable in serum over 4 h and exhibited a specific uptake of 18.04 ± 2.04% ID/g at 0.5 h after injection to high VEGFR-3 expressing A549 tumor mice. More importantly, lower uptake concentration in heart (1.06 ± 0.15% ID/g) after 2 h demonstrated the safety of peptide in vivo. The high uptake in the kidneys revealed that renal clearance was the main route of 131I-CP-7 peptide elimination from the body. Lower accumulation of 131I-CP-7 peptide in VEGFR-3 negative HeLa tumor mice further indicated that CP-7 p...Continue Reading

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Citations

Feb 21, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Qi Y WangYue Wang
May 1, 2019·International Journal of Molecular Sciences·Nikola ŠtambukMario Gabričević

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