In this study, we present the synthesis, self-assembly, and enzyme responsive nature of a unique class of well-defined amphiphilic linear-dendritic block copolymers (PNVP(Phe-Lys), n = 1-3) based on linear poly(-vinylpyrrolidone) (PNVP) and dendritic phenylalanyl-lysine (Phe-Lys) dipeptides. The copolymers were prepared via a combination ofreversible addition-fragmentation chain transfer (RAFT) /xanthates (MADIX) polymerization of -vinylpyrrolidone and stepwise peptide chemistry. The results of fluorescence spectroscopy, H NMR analyses, transmission electron microscopy (TEM), and particle size analysis demonstrated that the copolymers self-assemble in aqueous solution into micellar nanocontainers that can disassemble and release encapsulated anticancer drug doxorubicin or hydrophobic dye Nile red by trigger of a serine protease trypsin under physiological conditions. The disassembly of the formed micelles and release rates of the drug or dye can be adjusted by changing the generation of dendrons in PNVP(Phe-Lys). Furthermore, the cytocompatibility of the copolymers have been confirmed using human lung epithelial cells (BEAS-2B) and human liver cancer cells (SMMC-7721). Due to the fact of their enzyme responsive properties and good biocompatibility, the copolymers may have potential applicability in smart controlled release systems capable of site-specific response.