Po-207 ferritin-engineered nanoparticles as targeted drug delivery system for cancer treatment

Introduction Cancer remains still one of the major causes of death worldwide, therefore continuous improvements in tumor-fighting strategies are necessary. Targeting drugs directly to the tumour site, to overcome the systemic side effects, represents a great challenge. Nanoparticles have increasingly been used as drug delivery system showing intriguing therapeutic efficacies. Material and methods A genetically engineered nanocarrier based on human ferritin heavy chain (HFt) able to incorporate and deliver drugs was developed. These nanoparticles contain a short motif sequence (MP) cleavable by matrix metalloproteases between the HFt subunit and a masking sequence rich in proline (P), alanine (A) and serine (S): HFt-MP-PASE40. A topoisomerase I inhibitor was loaded into these nanocarriers (HFt-MP-PASE-Topo). Cell viability of different pancreatic cancer cell lines was evaluated in vitro . In vivo the therapeutic efficacy of HFt-MP-PASE-Topo was investigated on both a pancreatic cancer cell-line-derived xenograft and a patient-derived pancreatic cancer xenograft (PDX). Results and discussions In vitro studies showed a potent cytotoxic activity of HFt-MP-PASE-Topo with an IC50 that ranges between 0,005 µM to 0,05 µM. In vivo studies further demonstrated the therapeutic efficacy of HFt-MP-PASE-Topo in pancreatic cancer-bearing mice and in PDX model. In vivo treatments exhibited a robust decrease in tumour growth furthermore the animal overall survival significantly increased in HFt-MP-PASE-Topo treated mice. Conclusion Altogether, our results indicate that HFt-MP-PASE-Topo may constitute a promising tool in anticancer therapeutics.