Synthesis of a functionalized dipeptide for targeted delivery and pH-sensitive release of chemotherapeutics

Abstract

Targeted delivery of chemotherapeutics to tumor cells is one of the biggest challenges in cancer treatment. Herein, we synthesized smart dipeptide nanoparticles for cancer-specific targeting and intracellular pH-sensitive release of chemotherapeutics. Diphenylalanine peptide was synthesized and further developed as nanoparticles (NPs), which were functionalized with folic acid utilizing the carbodiimide reaction. Doxorubicin (Dox) was loaded to self-assembled non-functionalized (FF–Dox) and folate functionalized peptides NPs (FA–FF–Dox). Moreover, the experiments revealed the pH-sensitive release of Dox for both FA–FF–Dox and FF–Dox due to the protonation of the Schiff base and the amines present in the peptides at low pH, enhancing intracellular release subsequent to receptor-mediated endocytosis. Further, biodistribution and the pharmacokinetics study revealed enhanced targeting efficiency of FA–FF–Dox with high accumulation in tumor cells.