Ferritin-based anticancer metallodrug delivery: Encapsulation of Arsenoplatin-1 within the ferritin nanocage

An ideal drug delivery system is characterized by high stability, biocompatibility, suitable pharmacokinetics and selective delivery of cargo molecules to target cells. In this respect, molecules already present in the body, like proteins, are more acceptable and safer for the immune defense mechanism. Ferritins (Fts) are proteins that self-assemble into hollow cage-like structures. Fts have been used to encapsulate drugs, nutrients, photosensitizers and molecules for optical imaging, catalysis and photodynamic therapy. In the present work, horse spleen Ft was chosen to encapsulate Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)₂ core with a square planar Pt(II) and a five coordinate As(III) geometry.

AP-1 is very stable in solution and has a promising activity in drug-resistant cancer cell lines. AP-1-encapsulated Ft was prepared following the alkaline pH procedure previously used to produce cisplatin-encapsulated Ft. Briefly, the Ft cage is disassembled at basic pH and then reassembled in the presence of the drug by raising the pH at a neutral value. In this way, the metallodrug is trapped inside the Ft core. UV-Vis spectroscopy and ICP-OES measurements confirm the successful encapsulation and allow to evaluate the exact amount of AP-1 that is present within the Ft nanocage. The X-ray structure of AP-1-encapsulated Ft reveals that an AP-1 fragment without the chloride ligand binds the protein. The biological activity of AP-1-loaded Ft was tested on cancer cell lines and compared to that observed in normal ones. The results indicate that, even if reducing the overall drug toxicity, the presence of the cage improves AP-1 selectivity for cancer cells, since tumor cells appear more sensitive to the drug-loaded system when compared to normal cells.