Although fullerenes were discovered nearly three decades ago, the mechanism of their formation remains a mystery. Many versions of the classic 'bottom-up' formation mechanism have been advanced, starting with C 2 units that build up to form chains and rings of carbon atoms and ultimately form those well-known isolated fullerenes (for example, I h -C 60 ). In recent years, evidence from laboratory and interstellar observations has emerged to suggest a 'top-down' mechanism, whereby small isolated fullerenes are formed via shrinkage of giant fullerenes generated from graphene sheets. Here, we present molecular structural evidence for this top-down mechanism based on metal carbide metallofullerenes M 2 C 2 @C 1 (51383)-C 84 (M 5 Y, Gd). We propose that the unique asymmetric C 1 (51383)-C 84 cage with destabilizing fused pentagons is a preserved 'missing link' in the top-down mechanism, and in well-established rearrangement steps can form many wellknown, high-symmetry fullerene structures that account for the majority of solvent-extractable metallofullerenes.T he discovery of fullerenes 1 has opened up new vistas in nanoscience, and metallofullerenes have shown great promise in photovoltaic 2 and biomedical 3 applications. However, their formation mechanism remains unclear. Various versions of the 'bottom-up' mechanism have been posited as the main pathway for fullerene formation 4,5 , suggesting that fullerenes are formed by consecutively adding C 2 units to small carbon nanoclusters and cages. In recent years, with the development of graphene 6 , evidence has emerged to suggest a 'top-down' mechanism, whereby fullerene cages are formed via shrinkage of giant fullerene structures generated from graphene. One piece of direct evidence for the topdown mechanism is the reported laboratory transformation from graphene to fullerene 7 . It has also been demonstrated that fullerenes can be pyrolysed and lose carbon atoms to form smaller fullerenes at high temperature in an argon stream 8 . Another strong supporting argument for the top-down mechanism is that fullerenes are formed in the interstellar medium 9 by a photochemical process in which graphene sheets curve and lose C 2 and other fragments 10 . However, evidence for the top-down mechanism has not been demonstrated at the molecular level. Here, we present NMR spectroscopic and X-ray crystallographic structural characterization for M 2 C 2 @C 1 (51383)-C 84 (M ¼ Y, Gd) metallofullerenes. These molecules have a unique asymmetric cage C 1 (51383)-C 84 that represents the first characterized preserved intermediate suggesting top-down formation of fullerenes and metallofullerenes.The proposed top-down mechanism is illustrated in Fig. 1. Under appropriate conditions, graphene sheets can spontaneously roll and warp to form other nanostructures 11,12 , including randomly formed giant closed carbon networks-the primitive fullerene cages 7 . In an important computational study, a 'shrinking hot giant fullerene' mechanism that leads to smaller fullerene structures has been advan...

Water-soluble derivatives of gadolinium-containing metallofullerenes have been considered to be excellent candidates for new magnetic resonance imaging (MRI) contrast agents because of their high relaxivity and characteristic encapsulation of the lanthanide ions (Gd(3+)), preventing their release into the bioenvironment. The trimetallic nitride template endohedral metallofullerenes (TNT EMFs) have further advantages of high stability, high relative yield, and encapsulation of three Gd(3+) ions per molecule as illustrated by the previously reported nearly spherical, Gd3N@I(h)-C80. In this study, we report the preparation and functionalization of a lower-symmetry EMF, Gd3N@C(s)-C84, with a pentalene (fused pentagons) motif and an egg-shaped structure. The Gd3N@C84 derivative exhibits a higher (1)H MR relaxivity compared to that of the Gd3N@C80 derivative synthesized the same way, at low (0.47 T), medium (1.4 T), and high (9.4 T) magnetic fields. The Gd3N@C(s)-C84 derivative exhibits a higher hydroxyl content and aggregate size, as confirmed by X-ray photoelectron spectroscopy (XPS) and dynamic light scattering (DLS) experiments, which could be the main reasons for the higher relaxivity.

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Messenger RNA (mRNA)‐based vaccines have enormous potential in infectious disease prevention and tumor neoantigen application. However, developing an advanced delivery system for efficient mRNA delivery and intracellular release for protein translation remains a challenge. Herein, a biocompatible biomimetic system is designed using red blood cell‐derived nanoerythrosomes (NER) and black phosphorus nanosheets (BP) for mRNA delivery. BP is covalently modified with polyethyleneimine (PEI), serving as a core to efficiently condense mRNA via electrostatic interactions. To facilitate the spleen targeting of the mRNA‐loaded BP (BPmRNA), NER is co‐extruded with BPmRNA to construct a stable “core–shell” nanovaccine (NER@BPmRNA). The mRNA nanovaccine exhibits efficient protein expression and immune activation via BP‐mediated adjuvant effect and enhanced lysosomal escape. In vivo evaluation demonstrates that the system delivery of mRNA encoding coronavirus receptor‐binding domain (RBD) significantly increases the antibody titer and pseudovirus neutralization effect compared with that of NER without BP assistance. Furthermore, the mRNA extracted from mouse melanoma tissues is utilized to simulate tumor neoantigen delivered by NER@BPmRNA. In the vaccinated mice, BP‐assisted NER for the delivery of melanoma mRNA can induce more antibodies that specifically recognize tumor antigens. Thus, BP‐assisted NER can serve as a safe and effective delivery vehicle in mRNA‐based therapy.

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Pyroptosis is accompanied by immunogenic mediators’ release and serves as an innovative strategy to reprogram tumor microenvironments. However, damaged mitochondria, the origin of pyroptosis, are frequently eliminated by mitophagy, which will severely impair pyroptosis-elicited immune activation. Herein, black phosphorus nanosheets (BP) are employed as a pyroptosis inducer delivery and mitophagy flux blocking system since the degradation of BP could impair lysosomal function by altering the pH within lysosomes. The pyroptosis inducer of lonidamine (LND) was precoupled with the mitochondrial target moiety of triphenylphosphonium to facilitate the occurrence of pyroptosis. The mitochondria-targeting LND-modified BP (BPTLD) were further encapsulated into the macrophage membrane to endow the BPTLD with blood-brain barrier penetration and tumor-targeting capability. The antitumor activities of membrane-encapsulated BPTLD (M@BPTLD) were investigated using a murine orthotopic glioblastoma model. The results demonstrated that the engineered nanosystem of M@BPTLD could target the mitochondria, and induce as well as reinforce pyroptosis via mitophagy flux blocking, thereby boosting the release of immune-activated factors to promote the maturation of dendritic cells. Furthermore, upon near-infrared (NIR) irradiation, M@BPTLD induced stronger mitochondrial oxidative stress, which further advanced robust immunogenic pyroptosis in glioblastoma cells. Thus, this study utilized the autophagy flux inhibition and phototherapy performance of BP to amplify LND-mediated pyroptosis, which might greatly contribute to the development of pyroptosis nanomodulators.