Compared with physical drug-loaded nanocarriers,polymeric prodrug micelles have many advantages such as high drug loading and enhanced stability in blood,so they have great potential in cancer therapy.However,these micelles have a big disadvantage,which cannot achieve long-term circulation in vivo and high absorption of tumor cells simultaneously,resulting in low administration efficiency and poor ther-apeutic effect on cancer.To solve problems of traditional polymeric prodrug micelles,novel polymeric micelles with tumor microenvironment response were designed in this work.The prodrug formed by covalently linking D-α-tocopherol polyethylene glycol succinate (TPGS3350),peptide (Pep),and doxoru-bicin (DOX) (TPGS3350-Pep-DOX) was self-assembled into micelles by encapsulating DOX physically.When the micelles entered the tumor tissue,the long-chain polyethylene glycol (PEG) was sensitively cut by the matrix metalloproteinase 2/9 (MMP2/9) enzyme,exposing the targeting molecule folate,then it entered the cell through the endocytic pathway mediated by the folate receptor.The drug loading con-tent,encapsulation efficiency,critical micelle concentration,and invitro release of the micelles invented in this study were measured to characterize their properties.The particle size and zeta potential of micelles were characterized by dynamic light scattering.Images were scanned by transmission electron microscopes.In vitro cytotoxicity,cellular uptake,and in vivo antitumor effect evaluation experiments were measured to show that smart micelles have made much progress in material chemistry and drug delivery,making it possible to apply a stimulus-response carrier drug delivery system in clinical application.