Chemotherapy for breast cancer is significantly restricted by the tumor's physio-pathological complexity. Here we have constructed a targeted nano-system based on PEGylated poly (D, L-lactide) (PEG-PDLLA) using a novel ligand, CLKADKAKC (CK3) peptide, for active targeting to Neuropilin-1-rich breast cancer cells. CK3 increased the cellular uptake of micelles 4.7-fold compared with the free drug and nearly 2.2-fold compared with the unmodified micelles (PM), respectively. Furthermore, in vivo imaging revealed that CK3-modified micelles (CK3-PM) had excellent specific tumor cells targeting and the drug accumulation was also enhanced. When paclitaxel (PTX) was loaded into micelles, CK3-PM-PTX induced the strongest inhibition and apoptosis against MDA-MB-231 cells in vitro and in vivo. These results demonstrated that CK3-modified PEG-PDLLA micelles developed in this study could be a potential targeted vehicle for enhancing the chemotherapy of breast cancers.