Framework For Delivering Platinum Cancer Drugs

Platinum-based antitumor agents can hitch a ride into cancer cells via metal-organic framework compounds (MOFs), according to a new report (J. Am. Chem. Soc., DOI: 10.1021/ja803383k). Wenbin Lin and coworkers at the University of North Carolina, Chapel Hill, built the drug-delivering MOFs from terbium ion connectors and c,c,t-(diamminedichlorodisuccinato)Pt(IV) bridging ligands. They precipitated the amorphous nanoscale MOFs from an aqueous solution of the components simply by adding methanol. To prevent the MOFs from falling apart before they get to their final cellular destination, the researchers encapsulated them in amorphous silica. Lin’s team can control how quickly the MOFs release their Pt(IV) ligands—which rapidly convert into highly potent Pt(II) species inside cells—by varying the thickness of the silica shell. To ensure accurate delivery, the researchers decorated the exterior of the silica-coated MOFs with a cyclic pentapeptide that’s known to coax certain kinds of cancer cells to take in the peptide’s cargo via endocytosis. As expected, the peptide-marked MOFs selectively kill these kinds of cancer cells. The team suggests that analogous MOFs could be designed to deliver other therapeutic and imaging agents.