Bioinspired neuromelanin-like Pt(iv) polymeric nanoparticles for cancer treatment

Abstract

To expand the chemotherapeutic potential of platinum complexes, different approaches have been followed, two of the most relevant being their administration as the prodrug Pt(iv) and encapsulation in nanocarriers. Herein, we demonstrate how neuromelanin may become a good bioinspiration for the synthesis of nanoparticles (NPs), combining both approaches. For this, complex PtBC reacts with sodium periodate, inducing a melanization process and the formation of nanoparticles. In vitro results on non-malignant human fibroblast cells (1Br3G), human cervical cancer, murine glioma (GL261), and human ovarian cancer confirmed its therapeutic efficacy. The role of the Pt(iv) ion on the cytotoxicity effects was confirmed by comparison with the results obtained for a family of nanoparticles obtained with nordihydroguaiaretic acid under the same experimental conditions. Finally, intranasal administration of the NPs in orthotopic glioblastoma multiforme murine models in female C57BL/6 mice showed excellent in vivo biodistribution and tolerability. Overall, this innovative approach represents a step toward more specific and less toxic therapies in the field of cancer chemotherapy.