The Study Of Synergetic Liposomes Modified With Peptide On Tumor Imaging And Targeted Drug Delivery

ObjectAn effective drug delivery system for HER2(human epidermal growth factor receptor 2)positive cancer was constructed.HER2-specific peptide(named HE2)was screened from “One Bead One Conpound” peptide library using a microarray chip system.Liposomes modified with HER2-targeted peptide HE2(YDLKEPEH)and one cell-penetrating peptide TAT(GRKKRRQRRRPPQ)can show synergistic effect on tumor imaging and targeted drug delivery.It may be valuable for future clinical applications for HER2 positive breast cancer targeted therapy.MethodsUsing microarray chip system,a novel peptide probe(HE2)towards HER2 had been successfully screened out from a 106 “One Bead One Conpound”peptide library.By Surface Plasmon Resonance Imaging(SPRi)assay),the dissociation constants(KD)between HE2 and HER2 was calculated.The affinity of the peptide HE2 was examined at the cellular level using a confocal microscope.Then,based on the affinity peptide HE2 and TAT,we established four types of liposomes.They are mono-functionalized liposomes(HE2-LS,TAT-LS),traditional liposomes(LS),and synergetic liposomes(HE2/TAT-LS).The effects of four types of liposomes on drug delivery efficiency and tumor therapy were evaluated on cell level in vitro and animal level in vivo.ResultsUsing microarray chip system,a novel peptide probes(HE2)towards HER2 had been successfully screened out from a “One Bead One Conpound”peptide library.By Surface Plasmon Resonance Imaging(SPRi)assay),the dissociation constants(KD)between HE2 and HER2 was calculated as 3.9×10-8mol/L.From cells experiment,it is indicated that HE2 has high binding affinity and specificity towards HER2.Liposomes were prepared by thin film dispersion method.The size and zeta potential were measured by dynamic light scattering(DLS)and transmission electron microscope(TEM).The average diameter and the zeta potential of synergetic liposomes(HE2/TAT-LS-DOX),mono-functionalized liposomes(HE2-LS-DOX,TAT-LS-DOX,)and blank liposome were(154.7 nm,-13.8 m V),(157.6 nm,-14.0 m V),(150.3 nm,-13.6m V)and(140.2 nm,-12.8 m V),respectively.Furthermore,DOX encapsulation efficiency was also calculated as 81.26% of HE2/TAT-LS-DOX,80.36% of TAT-LS-DOX,80.48% of HE2-LS-DOX and 79.35% of LS-DOX.In vitro on cellular level,it shown synergetic liposomes was an efficient nanocarries for drug delivery towards HER2-positive cancer cells.In vivo animal experiment,synergetic liposomes exhibited the highest fluorescent signal in tumor sites and showed a good tumor inhibition effect.ConclusionsIn this study,from “One Bead One Conpound” peptide library,positive peptides HE2 were selected by using a microarray device.Moreover,we successfully established multi-functionalized liposomes modi?ed with a novel HER2 affinity peptide(HE2)and the cell-penetrating peptide TAT simultaneously.This functionalized nanoscaled delivery system can reduce the side effects of chemotherapy drugs,and increase the therapeutic effect of the drugs.It may be valuable for future clinical applications for HER2 positivebreast cancer targeted therapy.