A Tumor Homing Peptide-Conjugated Poly(epsilon-lysine) Delivery System for Improved Antitumor Drug Loading and Targeting

The main challenges with conventional chemotherapeutic drugs are their non-selective toxicity and limited targeting abilities. Hence, it is imperative to employ a specific targeting drug delivery system (DDS) to improve their specificity with a potential activity. This study aims to enhance antitumor delivery, loading and targeting via functionalization of a poly lysine carrier system with a tumor-homing peptide, CREKA. Solid phase peptide synthesis was employed in the synthesis, and mass spectra and HPLC techniques were used for characterization. The cytotoxicity on tumor and normal cells was assessed via a cell viability test and degradation rate with cellular uptake by confocal microscopy and flow cytometry were also studied. Biochemical enzymatic inhibition assay on dihydrofolate reductase (DHFR), the target enzyme, was conducted to study the efficacy of the drug-loaded DDS. The results confirmed successful synthesis and conjugation of the drug with this DDS with high effectiveness against cytotoxicity and inhibition of DHFR. Results also revealed a high degradation rate at the acidic pH and cellular internalization. It can be concluded that the CREKA-functionalized DDS has delivered the drug to the target tumor cells, reducing its localization in normal cells with a higher loading capacity. Thus, the study demonstrated the significant contribution of the designed carrier in the therapeutic interventions in cancer.