Screening, Identification, Application Of Tumor-targeting Peptides With Neuropilin-1

Objective:Neuropilin-1is over-expressed and associated with poor out-come in breastcancer. The aim of this work is to identify a neuropilin-1targeting peptide fornear-infrared fluorescence and SPECT imaging of breast cancer.Methods: Screening was carried out with a9amino acid phage display peptide libraryagainst neuropilin-1positive breast cancer MDA-MB-231cells. A neuropilin-1targeting peptide was identified and validated by cellular ELISA and DNA sequencing.In vivo and in vitro experiments showed that the CK3bind to neuropilin-1(NRP-1) onthe target cells. After radiolabeled with99mTc, the peptide was used in SPECT imagingin mice bearing MDA-MB-231tumors.Results：An enrichment of phages bound to MDA-MB-231cells was obtained in threerounds of screening. A neuropilin-1targeting CLKADKAKC peptide containing acryptic C-end rule motif was identified. In vitro studies revealed that this peptide onlybond to but did not penetrate into neuropilin-1positive cells. In vivo distributionstudies demonstrated that Cy5and99mTc labeled CLKADKAKC peptide homed totumors in mice bearing MDA-MB-231tumors.Conclusions:（1）Screening of a receptor-specific targeting Neuropilin1-expressingBreast Carcinoma Cells polypeptide for binding by phage display；（2）In vivo and invitro experimentsshowed that the CK3bind to neuropilin-1(NRP-1) on the target cells； （3）Near-infrared fluorescence and SPECT imaging with a neuropilin-1targetingpeptide in breast cancer。...