Metallofullerene Nanoparticles in Biomedical Applications

Metallofullerene nanoparticles, comprising carbon cages that encapsulate metal atoms or clusters, have emerged as a versatile class of nanomaterials for diagnosis and therapy. Their unique architecture combines the physicochemical stability and electron affinity of fullerenes with the functional properties of endohedral metals, yielding agents that can serve as contrast media, drug carriers and bioactive inhibitors. In magnetic resonance imaging (MRI), gadolinium‐containing metallofullerenes offer superior proton relaxivity at reduced doses, enhancing image sensitivity while minimising toxicity. Beyond imaging, specific metallofullerene derivatives exhibit intrinsic therapeutic activity: certain formulations block key signalling pathways in cancer stem cells, whereas others scavenge reactive oxygen species to protect healthy tissues during chemotherapy. Advances in surface modification and supramolecular assembly have improved water solubility, biocompatibility and targeted delivery, overcoming long-standing challenges of hydrophobicity and off‐target accumulation. Collectively, metallofullerene nanoparticles exemplify a platform capable of integrating diagnosis and therapy into single nanostructures, with implications for precision healthcare across oncology, neurology and beyond.

Research from Nature Portfolio

Recent studies have demonstrated the power of metallofullerene design in both imaging and direct cancer intervention. A tri-gadolinium nitride fullerene conjugated to a tumour-homing peptide achieved high‐contrast MRI of aggressive breast tumours at micromolar doses, enabling non-invasive risk stratification of high-risk lesions. In parallel, a hydroxylated Gd@C82 derivative was shown to inhibit epithelial-to-mesenchymal transition in triple-negative breast cancer, selectively eradicating cancer stem cells by dual blockade of hypoxia-inducible and transforming growth factor-β pathways without harming normal epithelial cells. Complementing these, amino-acid-grafted C70 fullerenes have been developed as powerful radical scavengers that protect cardiac and hepatic tissue from chemotherapy-induced oxidative injury, illustrating how tailored fullerene cages can serve as “bodyguards” during cytotoxic treatment. These contributions underscore the dual capacity of metallofullerenes to advance molecular imaging and exert direct therapeutic effects.

Metallofullerene Nanoparticles in Biomedical Applications publication trend

The graph below shows the total number of articles in metallofullerene nanoparticles in biomedical applications across all publications each year (not limited to Nature Index journals).

Technical terms

Metallofullerene: A nanoscale carbon cage (fullerene) encapsulating one or more metal atoms or clusters, combining carbon’s stability with metal functionalities.

Endohedral functionalisation: The process of introducing atoms or molecules inside the fullerene cage, altering electronic and magnetic properties without disrupting the exterior surface.

Relaxivity: A measure of a contrast agent’s efficiency in shortening proton relaxation times in MRI, indicating image‐enhancing potency.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen, involved in cell signalling but capable of causing oxidative damage when in excess.

Supramolecular assembly: The organised association of molecules through noncovalent interactions, used to construct hierarchical nanostructures for controlled drug delivery.

References

1. Ferritin‐Based Supramolecular Assembly Drug Delivery System for Aminated Fullerene Derivatives to Enhance Tumor‐Targeted Therapy. Advanced Science (2024).
2. Targeted gadofullerene for sensitive magnetic resonance imaging and risk-stratification of breast cancer. Nature Communications (2017).
3. Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor. Nature Communications (2015).
4. Amino acid modified [70] fullerene derivatives with high radical scavenging activity as promising bodyguards for chemotherapy protection. Scientific Reports (2018).
5. Structurally Defined Water‐Soluble Metallofullerene Derivatives towards Biomedical Applications. Angewandte Chemie International Edition (2022).
6. Metallofullerenols in biomedical applications. European Journal of Medicinal Chemistry (2022).
7. Gadolinium‐containing carbon nanomaterials for magnetic resonance imaging: Trends and challenges. Journal of Cellular and Molecular Medicine (2020).