biostudies-literatureLi YGeneralitat de CatalunyaU.S. Department of EnergyResearch Council, Rutgers, The State University of New JerseyNIH Office of the DirectorNIDCD NIH HHSMinisterio de Ciencia e InnovaciónNIAMS NIH HHSNational Science Foundatione202211704https://www.ebi.ac.uk/biostudies/studies/S-EPMC9983306biostudies-literatureUnknown62(3)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 T₁ 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.Angewandte Chemie (International ed. in English)Structurally Defined Water-Soluble Metallofullerene Derivatives towards Biomedical Applications.PMC9983306R01 DC016612CHE-14290621R01DC016612R21 AR071101PID2020-112762GB-I003R01DC016612-01S12017SGR629R21AR071101Juan de la Cierva FellowshipDMR-1644779DE-SC00202605R01DC016612-02S1CBET-1803517Busch Biomedical GrantHill SYang LAbella LLee KBZhang JCrichton RARodriguez-Fortea ADubroca TSun YLi YKopcha WPKundu KBiswas RYeh YWPoblet JMRathnam CfalseStructurally 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 T₁ 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.2023-01-01T00:00:00Z2023 Jan2026-03-17T16:00:07.342Z2025-04-04T03:20:27.813ZS-EPMC99833063634940510.1002/anie.202211704