Search

Autoimmune hepatitis (AIH) is a severe immune-mediated inflammatory liver disease whose standard of care is immunosuppressive treatment with inevitable undesired outcomes. Macrophage is acknowledged to aggravate liver damage, providing a promising AIH therapeutic target. Accordingly, in this study, a kind of curdlan-decorated fullerene nanoparticle (Cur-F) is fabricated to alleviate immune-mediated hepatic injury for treating AIH via reducing macrophage infiltration in a concanavalin A (Con A)-induced AIH mouse model. After intravenous administration, Cur-F primarily distributes in liver tissues, efficiently eliminates the excessive reactive oxygen species, significantly attenuates oxidative stress, and subsequently suppresses the nuclear factor kappa-B-gene binding (NF-κB) signal pathway, resulting in the lowered production of pro-inflammatory cytokines and the balancing of the immune homeostasis with the prevention of macrophage infiltration in the liver. The regulation of hepatic inflammation contributes to inhibiting inflammatory cytokines-induced hepatocyte apoptosis, decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) contents and thus ameliorating immune-mediated hepatic injury. Notably, there is no detectable toxicity to the body. Our findings may open up novel avenues for AIH based on curdlan and fullerene materials.

Photothermal therapy (PTT) triggered by near-infrared-II (NIR-II, 1000-1700 nm) light is developed as a potential tumor therapy technique with deeper tissue penetration capacity and higher allowable laser power density of the skin than NIR-I (750-1000 nm) biowindow. Black phosphorus (BP) with excellent biocompatibility and favorable biodegradability demonstrates promising applications in PTT but suffers from low ambient stability and limited photothermal conversion efficiency (PCE), and utilization of BP in NIR-II PTT is scarcely reported. Herein, we develop novel fullerene covalently modified few-layer BP nanosheets (BPNSs) with ∼9-layer thickness through an easy one-step esterification process (abbreviated BP-ester-C 60 ), bringing about the dramatically enhanced ambient stability of BPNSs due to bonding of the hydrophobic C 60 with high stability and the lone electron pair on the phosphorus atom. BP-ester-C 60 is then applied as a photosensitizer in NIR-II PTT, delivering a much higher PCE than the pristine BPNSs. Under 1064 nm NIR-II laser irradiation, in vitro and in vivo antitumor studies reveal that BP-ester-C 60 exhibits dramatically enhanced PTT efficacy with considerable biosafety relative to the pristine BPNSs. This is interpreted by the boost of NIR light absorption on account of the modulation of the band energy level resulting from intramolecular electron transfer from BPNSs to C 60 .

Functional fullerene derivatives exhibit fantastic inhibitory capabilities against cancer survival and metastasis, but the absence of clarified biological molecular targets and ambiguous regulation mechanisms set barriers for their clinical transformation. Cancer metastasis is the primary cause of mortality and initiated with increased cell migration, making cell motility regulation a high-value therapeutic target in precision medicine. Herein, a critical molecular target of the aminated fullerene derivative (C 70 -EDA), myosin heavy chain 9 (MYH9), was initially identified by a pull-down assay and MS screening. MYH9 is a cytoplasm-located protein and is responsible for cell motility and epithelial-mesenchymal transition regulation. Omics data from large-scale clinical samples reveals that MYH9 gets overexpressed in various cancers and correlates with unfavorable prognosis, indicating that it is a potential antineoplastic target. It is unveiled that C 70 -EDA binds to the C-terminal of MYH9, triggering the transport of MYH9 from the cytoplasm to the cell edge, blocking the MYH9-involved cell mobility, and inhibiting the metastasis-associated EMT process. This work provides a precise biological target and new strategies for fullerene applications in cancer therapy.

Nowadays, determining the disassembly mechanism of amyloids under nanomaterials action is a crucial issue for their successful future use in therapy of neurodegenerative and overall amyloid-related diseases. In this study, the antiamyloid disassembly activity of fullerenes C 60 and C 70 dispersed in 1-methyl-2-pyrrolidinone (NMP) toward amyloid fibrils preformed from lysozyme and insulin was investigated using a combination of different experimental techniques. Thioflavin T fluorescence assay and atomic force microscopy were applied for monitoring of disaggregation activity of fullerenes. It was demonstrated that both types of fullerene-based complexes are very effective in disassembling preformed fibrils, and characterized by the low apparent half-maximal disaggregation concentration (DC 50 ) in the range of ∼22-30 μg mL -1 . Small-angle neutron scattering was employed to monitor the different stages of the disassembly process with respect to the size and morphology of the aggregates. Based on the obtained results, a possible disassembly mechanism for amyloid fibrils interacting with fullerene/NMP complexes was proposed. The study is a principal step in understanding of the fullerenes destruction mechanism of the protein amyloids, as well as providing valuable information on how macromolecules can be engineered to disassemble unwanted amyloid aggregates by different mechanisms.

We report the construction of blood cell membrane cloaked mesoporous silica nanoparticles for delivery of nanoparticles [fullerenols (Fols)] with fibrinolysis activity which endows the active Fol with successful thrombolysis effect in vivo . In vitro , Fols present excellent fibrinolysis activity, and the Fol with the best fibrinolysis activity is screened based on the correlation between Fols' structure and their fibrinolysis activity. However, the thrombolytic effect in vivo is not satisfactory. To rectify the unsatisfactory situation and avoid the exogenous stimuli, a natural blood cell membrane cloaking strategy with loading the active Fol is chosen to explore as a novel thrombolysis drug. After cloaking, the therapeutic platform prolongs blood circulation time and enhances the targeting effect. Interestingly, compared with platelet membrane cloaking, red blood cell (RBC) membrane cloaking demonstrates stronger affinity with fibrin and more enrichment at the thrombus site. The Fol with RBC cloaking shows quick and efficient thrombolysis efficacy in vivo with less bleeding risk, more excellent blood compatibility, and better biosafety when compared with the clinical drug urokinase (UK). These findings not only validate the blood cell membrane cloaking strategy as an effective platform for Fol delivery on thrombolysis treatment, but also hold a great promising solution for other active nanoparticle deliveries in vivo .

Along with the rapid appearance of superbacteria with multidrug resistance, it is a challenge to develop new antibacterial materials to address this big issue. Herein, we report a novel amine group-modified fullerene derivative (C 70 -(ethylenediamine) 8 abrr. C 70 -(EDA) 8 ), which reveals a high performance in killing superbacteria, and most importantly, it shows negligible toxicity to the mammalian cells. The strong antibacterial ability of this material was attributed to its unique molecular structure. On one hand, amino groups on the EDA part make it easy to affix onto the outer membrane of multidrug resistance Escherichia coli by electrostatic interactions. On the other hand, the hydrophobic surface on the C 70 part makes it easy to form a strong hydrophobic interaction with the inner membrane of bacteria. Finally, C 70 -(EDA) 8 leads to the cytoplast leakage of superbacteria. In contrast, the C 70 -(EDA) 8 is nontoxic for mammalian cells due to different distributions of the negative charges in the cell membrane. In vivo studies indicated that C 70 -(EDA) 8 mitigated bacterial infection and accelerated wound healing by regulating the immune response and secretion of growth factors. Our amine group-based fullerene derivatives are promising for clinical treatment of wound infection and offer a new way to fight against the superbacteria.

Titanium dioxide nanomaterials have good capability to prevent human cells from damage under UV irradiation. However, some studies indicated that the nanoscale of titanium dioxide could potentially cause harmful effects such as free radical generation under UV irradiation and thereby accelerate the progress of cell aging. Fullerenes can scavenge large amounts of free radicals due to the fact that fullerenes contain enormous amount of π electrons with low lying lowest unoccupied molecular orbital, but its adverse properties, such as the poor solubility in water, restricted the applicability. In this study, we employed water-soluble carboxylic acid fullerenes (C 60 -COOH and C 70 -COOH) as the free radical scavenger and modify onto the surface of titanium dioxide by refluxed esterification (P25/C 60 -COOH or C 70 -COOH) technique. The conformation and properties of these nanomaterials were characterized by techniques and equipment such as X-ray diffraction, energy dispersive spectroscopy analysis, scanning electron microscopy, thermal gravimetric analysis, high-resolution transmission electron microscopy, and Fourier transform infrared spectroscopy. We also introduced methylene blue and rhodamine B as indicators to evaluate and demonstrate the scavenging capacity of these nanomaterials. Moreover, we examined the biocompatibility and UV protection capacity of our P25/fullerene composites in human 293T cells, and applied luciferase activity assay to investigate the possible underlying cell protection mechanisms exhibited by these nanomaterials. Our data indicate that both P25/C 60 -COOH and P25/C 70 -COOH could protect human cells against UV exposure. P25/C 70 -COOH exhibits great anti-inflammation capacity, whereas P25/C 60 -COOH exhibits great anti-oxidative stress and anti-DNA damage capacity. Our results suggest that most of our P25/fullerene composite materials have the ability to reduce free radicals and exhibit high biomedical potential in anti-inflammation, anti-oxidant, and anti-aging applications.

Oxidative stress induced by excessive production of reactive oxygen species (ROS) has been implicated in the etiology of many human diseases. Acquiring a highly efficient antioxidant with good biocompatibility is of significance in eliminating the deleterious effect induced by the oxidative stress. Herein, we address our efforts on investigating the cytoprotective effect of carboxyfullerenes on H2O2-injured cells. Meanwhile, the uptake and intracellular location of carboxyfullerenes were studied. The results show that C70-carboxyfullerenes (dimalonic acid C70 fullerene (DF70) and trimalonic acid C70 fullerene (TF70)) exhibit an obviously protective effect against oxidative stress on C2C12 cells at concentrations as low as 2.5 μmol L(-1), whereas C60-carboxyfullerenes (dimalonic acid C60 fullerene (DF60) and quadri-malonic acid C60 fullerene (QF60)) show a protective effect at relatively higher concentration (40 μmol L(-1)). The molecular structure of carboxyfullerenes and the physiological state of cells play an important role in the different cytoprotective capability. Further study reveals that DF70 and TF70 could enter into cells and mainly localize into the lysosome, which possibly involves the protective mechanism by stabilizing lysosome. The use of a significantly low concentration of C70-carboxyfullerene as the antioxidative agent will benefit the therapeutic approaches aiming at alleviating ROS-induced injuries such as muscle disorder and arthritis.

Satellite muscle cells play an important role in regeneration of skeletal muscle. However, they are particularly vulnerable to oxidative stress. Herein, we address our efforts on the cytoprotective activities of carboxyfullerenes with different cage size (C60 vs C70) and adduct number on postmitotic muscle cell (C2C12 cell). The correlation of the structural effect on the cytoprotective capability of carboxyfullerenes was evaluated. We find that quadri-malonic acid C70 fullerene (QF70) exhibits higher capability on protecting cells from oxidative-induced stress among these tested carboxyfullerenes. The accumulation of intracellular superoxide dismutase (SOD) is proposed to play an important role in their diverse antioxidative ability. Moreover, the pretreatment of QF70 could also obviously enhance the viability of myotubes originated from oxidative-stressed C2C12 cells, which facilitates the future application of carboxyfullerenes in tissue engineering and nanomedicine.

The adhesive properties, as measured by bulk tack analysis, are found to decrease in blends of isomerically pure Sc3N@I(h)-C80 metallic nitride fullerene (MNF) and polystyrene-block-polyisoprene-block-polystyrene (SIS) copolymer pressure-sensitive adhesive under white light irradiation in air. The reduction of tack is attributed to the in situ generation of 1O2 and subsequent photooxidative cross-linking of the adhesive film. Comparisons are drawn to classical fullerenes C60 and C70 for this process. This work represents the first demonstration of 1O2 generating ability in the general class of MNFs (M3N@C80). Additional support is provided for the sensitizing ability of Sc3N@I(h)-C80 through the successful photooxygenation of 2-methyl-2-butene to its allylic hydroperoxides in benzene-d(6) under irradiation at 420 nm, a process that occurs at a rate comparable to that of C(60). Photooxygenation of 2-methyl-2-butene is found to be influenced by the fullerene sensitizer concentration and O2 flow rate. Molar extinction coefficients are reported for Sc3N@I(h)-C80 at 420 and 536 nm. Evaluation of the potential antimicrobial activity of films prepared in this study stemming from the in situ generation of 1O2 led to an observed 1 log kill for select Gram-positive and Gram-negative bacteria.