Molecules, Vol. 25, Pages 484: Small Peptide-Doxorubicin Co-Assembly for Synergistic Cancer Therapy (Molecules)

Design of elaborated nanomaterials to improve the therapeutic efficacy and mitigate the side effects of chemotherapeutic anticancer drugs, such as Doxorubicin (Dox), is significant for cancer treatment. Here, we describe a co-assembled strategy, where amphiphile short peptides are co-assembled with Doxorubicin to form nanoscale particles for enhanced delivery of Dox. Two kinds of short peptides, Fmoc-FK (FK) and Fmoc-FKK (FKK), are synthesized. Through adjusting the component ratio of peptide and Dox, we obtain two kinds of co-assembled nanoparticles with homogeneous size distributions. These nanoparticles show several distinct characteristics. First, they are pH-responsive as they are stable in alkaline and neutral conditions, however, de-assembly at acidic pH enables selective Dox release in malignant cancer cells. Second, the nanoparticles show an average size of 50–100 nm with positive charges, making them effective for uptake by tumor cells. Moreover, the side effects of Dox on healthy cells are mitigated due to decreased exposure of free-Dox to normal cells. To conclude, the co-assembled peptide-Dox nanoparticles exhibit increased cellular uptake compared to free-Dox, therefore causing significant cancer cell death. Further apoptosis and cell cycle analysis indicates that there is a synergistic effect between the peptide and Doxorubicin.