Prostate cancer (PC) is the most common cancer in men over the age of 50 and the 4th most prevalent human malignancy. The current modalities to treat PC include surgery, radiation, androgen deprivation therapy (ADT) and chemotherapy. The therapeutic efficacy of systemic drug treatment is limited due to low drug solubility and lack of tumor specificity inflicting toxic side effects, and frequent emergence of drug-resistance. Herein we present selectively PC-targeted nanoparticles (NPs) harboring cytotoxic drugs cargo. The delivery system is based on PEGylated nanostructured lipid carriers, decorated with a selective peptide, targeted to prostate-specific membrane antigen (PSMA). NPs loaded with a chemotherapeutic drug, displayed remarkable encapsulation capacity of 168±3 mg drug/gr shell material, encapsulation efficiency of 67±1%, and an average diameter of 148±4 nm. The kinetics of in vitro drug release from NPs showed a substantial drug retention profile compared to unencapsulated drug. These NPs were selectively internalized into target PC cells overexpressing PSMA and displayed a dose-dependent cytotoxicity, compared to cells lacking PSMA receptor. This selectively targeted nano-delivery platform bear promise for achieving enhanced efficacy and minimization of untoward toxicity, thus should improve patient survival rates and quality of life.