Structurally Defined Water-Soluble Metallofullerene Derivatives towards Biomedical Applications

Endohedral metallofullerenes (EMFs) are excellent carriers of rare-earth element (REE) ions in biomedical applications because they preclude the release of toxic metal ions. However, existing approaches to synthesize water-soluble EMF derivatives yield mixtures that inhibit precise drug design. Here we report the synthesis of metallobuckytrio (MBT), a three-buckyball system, as a modular platform to develop structurally defined water-soluble EMF derivatives with ligands by choice. Demonstrated with PEG ligands, the resulting water-soluble MBTs show superb biocompatibility. The Gd MBTs exhibit superior T-1 relaxivity than typical Gd complexes, potentially superseding current clinical MRI contrast agents in both safety and efficiency. The Lu MBTs generated reactive oxygen species upon light irradiation, showing promise as photosensitizers. With their modular nature to incorporate other ligands, we anticipate the MBT platform to open new paths towards bio-specific REE drugs.

Automated summary

We report the synthesis of a three-buckyball metal complex (MBT) as a modular platform to develop water-soluble EMF derivatives. The resulting water-soluble MBTs show excellent biocompatibility and have potential applications in biomedical fields. The Gd MBTs exhibit superior T-1 relaxivity, while the Lu MBTs show promise as photosensitizers. We anticipate that the modular nature of the MBT platform will enable the development of bio-specific REE drugs.