Enhancing the anticancer effect of paclitaxel by using polymeric nanoparticles decorated with colorectal cancer targeting CPKSNNGVC-peptide

The major disadvantage of cancer chemotherapy is its lack of specificity. In recent years, selective delivery of chemotherapeutic agents to tumor sites has evolved rapidly in the form of both diagnostic and therapeutic tools in combating cancer. Herein, we develop a new polymeric nanoparticle delivery system that targets both monocarboxylate transporter 1 (MCT1) receptor-positive cancer cells and angiogenic endothelial cells using a tumor homing peptide (CPKSNNGVC, CPK in short) as a nanoparticle surface-bound targeting ligand. By using an emulsion-solvent evaporation method, multipotent drug paclitaxel (PTX)-encapsulated poly ( dl -lactide- co -glycolide) (PLGA) nanoparticles (diameter of 215 ± 4 nm; zeta potential of −12 ± 3 mV; 16–17.5% w/w PTX) were synthesized. CPK peptide was thereafter conjugated to the surface of nanoparticles via maleimide-thiol chemistry (CPK-PTX-NPs). Importantly, the highly stable CPK-PTX-NPs exhibited MCT1 receptor-mediated cellular uptake and apoptosis-mediated cell death in MCT1 receptor-overexpressing colorectal cancer (CRC) cells, while the other nontargeting nanoparticles failed to show MCT1 receptor-mediated cellular uptake. Remarkably, the targeted CPK-PTX-NPs selectively inhibited the formation of new blood vessels from pre-existing blood vessels (angiogenesis) in a chick embryo angiogenesis assay. In conclusion, our findings show that MCT1 receptor-selective, PTX-encapsulated and CPK peptide-decorated polymeric nanoparticles act as effective carriers for CRC-specific delivery of antineoplastic drugs to ensure significantly enhanced therapeutic efficacy.