Peptideligand-modifiednanomedicinesfortargetingcellsatthetumormicroenvironment☆AyeletDavid⁎DepartmentofClinicalBiochemistryandPharmacology,FacultyofHealthSciences,andtheIlseKatzInstituteforNanoscaleScienceandTechnology,Ben-GurionUniversityoftheNegev,Beer-Sheva8410501,IsraelabstractarticleinfoArticlehistory:Received22December2016Receivedinrevisedform17March2017Accepted9May2017Availableonline12May2017Sincetheirinitialdiscoverymorethan30yearsago,tumor-homingpeptideshavebecomeanincreasinglyusefultoolfortargeteddeliveryoftherapeuticanddiagnosticagentsintotumors.Today,itiswellacceptedthatcellsatthetumormicroenvironment(TME)contributeinmanywaystocancerdevelopmentandpro-gression.Tumor-homingpeptide-decoratednanomedicinescaninteractspecificallywithsurfacereceptorsexpressedoncellsintheTME,improvecellularuptakeofnanomedicinesbytargetcells,andimpairtumorgrowthandprogression.Moreover,peptideligand-modifiednanomedicinescanpotentiallyaccumulateinthetargettissueathigherconcentrationsthanwouldsmallconjugates,thusincreasingoveralltargettissueexposuretothetherapeuticagent,enhancetherapeuticefficacyandreducesideeffects.ThisreviewdescribesthemoststudiedpeptideligandsaimedattargetingcellsintheTME,discussesmajorobstaclesandprinciplesinthedesignofligandsfordrugtargetingandprovidesanoverviewofhomingpeptidesinligand-targetednanomedicinesthatarecurrentlyindevelopmentforcancertherapyanddiagnosis.©2017PublishedbyElsevierB.V.Keywords:CancertherapyDrugdeliverysystemsDrugtargetingNanomedicinesPeptideligandsTumor-homingpeptidesContents1.Introduction..............................................................1212.Targetingthetumormicroenvironment..................................................1213.Peptideliganddiscovery.........................................................1223.1.Focusedantibodylibraries.....................................................1233.2.One-bead–one-compoundpeptide(OBOC)libraries.........................................1233.3.Phagedisplaylibraries.................
