Jinquan Dong

The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials

We demonstrated that three different types of water-soluble fullerenes materials can intercept all of the major physiologically relevant ROS. C(60)(C(COOH)(2))(2), C(60)(OH)(22), and Gd@C(82)(OH)(22) can protect cells against H(2)O(2)-induced oxidative damage, stabilize the mitochondrial membrane potential and reduce intracellular ROS production with the following relative potencies: Gd@C(82)(OH)(22)> or =C(60)(OH)(22)>C(60)(C(COOH)(2))(2). Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O(2)(*-)), singlet oxygen, and hydroxyl radical (HO(*)), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities support the hypothesis that both chemical properties, such as surface chemistry induced differences in electron affinity, and physical properties, such as degree of aggregation, influence the biological and biomedical activities of functionalized fullerenes. This represents the first report that different types of fullerene derivatives can scavenge all physiologically relevant ROS. The role of oxidative stress and damage in the etiology and progression of many diseases suggests that these fullerene derivatives may be valuable in vivo cytoprotective and therapeutic agents.

The effect of Gd@C82(OH)22 nanoparticles on the release of Th1/Th2 cytokines and induction of TNF-α mediated cellular immunity

It is known that down-regulation of the immune response may be associated with the progenesis, development and prognosis of cancer or infectious diseases. Up-regulating the immune response in vivo is therefore a desirable strategy for clinical treatment. Here we report that poly-hydroxylated metallofullerenol (Gd@C(82)(OH)(22)) has biomedical functions useful in anticancer therapy arising from immunomodulatory effects observed both in vivo and in vitro. We found that metallofullerenol can inhibit the growth of tumors, and shows specific immunomodulatory effects on T cells and macrophages. These effects include polarizing the cytokine balance towards Th1 (T-helper cell type 1) cytokines, decreasing the production of Th2 cytokines (IL-4, IL-5 and IL-6), and increasing the production of Th1 cytokines (IL-2, IFN-gamma and TNF-alpha) in the serum samples. Immune-system regulation by this nanomaterial showed dose-dependent behavior: at a low concentration, Gd@C(82)(OH)(22) nanoparticles slightly affected the activity of immune cells in vitro, while at a high concentration, they markedly enhanced immune responses and stimulated immune cells to release more cytokines, helping eliminate abnormal cells. Gd@C(82)(OH)(22) nanoparticles stimulated T cells and macrophages to release significantly greater quantities of TNF-alpha, which plays a key role in cellular immune processes. Gd@C(82)(OH)(22) nanoparticles are more effective in inhibiting tumor growth in mice than some clinical anticancer drugs but have negligible side effects. The underlying mechanism for high anticancer activity may be attributed to the fact that this water-soluble nanomaterial effectively triggers the host immune system to scavenge tumor cells.

Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor

The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C82(OH)22, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C82(OH)22 blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C82(OH)22 mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C82(OH)22 is facilitated where it functions as a bi-potent inhibitor of HIF-1α and TGF-β activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol is identified as a kind of non-toxic CSC specific inhibitors with significant therapeutic potential.

Polyhydroxylated Metallofullerenols Stimulate IL‐1β Secretion of Macrophage through TLRs/MyD88/NF‐κB Pathway and NLRP3 Inflammasome Activation

Polyhydroxylated fullerenols especially gadolinium endohedral metallofullerenols (Gd@C82(OH)22) are shown as a promising agent for antitumor chemotherapeutics and good immunoregulatory effects with low toxicity. However, their underlying mechanism remains largely unclear. We found for the first time the persistent uptake and subcellular distribution of metallofullerenols in macrophages by taking advantages of synchrotron-based scanning transmission X-ray microscopy (STXM) with high spatial resolution of 30 nm. Gd@C82(OH)22 can significantly activate primary mouse macrophages to produce pro-inflammatory cytokines like IL-1β. Small interfering RNA (siRNA) knockdown shows that NLRP3 inflammasomes, but not NLRC4, participate in fullerenol-induced IL-1β production. Potassium efflux, activation of P2X7 receptor and intracellular reactive oxygen speciesare also important factors required for fullerenols-induced IL-1β release. Stronger NF-κB signal triggered by Gd@C82(OH)22 is in agreement with higher pro-IL-1β expression than C60(OH)22. Interestingly, TLR4/MyD88 pathway but not TLR2 mediates IL-1β secretion in Gd@C82(OH)22 exposure confirmed by macrophages from MyD88(-/-)/TLR4(-/-)/TLR2(-/-) knockout mice, which is different from C60(OH)22. Our work demonstrated that fullerenols can greatly activate macrophage and promote IL-1β production via both TLRs/MyD88/NF-κB pathway and NLRP3 inflammasome activation, while Gd@C82(OH)22 had stronger ability C60(OH)22 due to the different electron affinity on the surface of carbon cage induced by the encaged gadolinium ion.

An organic–inorganic hybrid perovskite logic gate for better computing

A practicable means of significantly reducing the energy consumption and speeding up the operating rate of computer chips is to place the processor and memory into one device, which processes and stores information simultaneously like the human brain. Here we demonstrate a novel sandwich architecture where organic–inorganic hybrid perovskite materials could be used as building-block materials for non-volatile memristors, accompanied with photoresponsive performance. Owing to the distinct photo-response of the two resistance states of the memristor, it is feasible to utilize the device as a logic OR gate by employing an electrical field and light illumination as input sources. This study provides potential applications in logic circuits, optical digital computation and optical quantum information for beneficial supplementation of the von Neumann architecture, or even for computing beyond it.

Novel Carbon Nanohybrids As Highly Efficient Magnetic Resonance Imaging Contrast Agents

Novel carbon nanohybrids based on unmodified metallofullerenes have been successfully fabricated for use as a new magnetic resonance imaging (MRI) contrast agent. The nanohybrids showed higher R1 relaxivity and better brightening effect than Gd@C82(OH)X, in T1-weighted MR images in vivo. This is a result of the proton relaxivity from the original gadofullerenes, which retained a perfect carbon cage structure and so might completely avoid the release of Gd3+ ions. A “secondary spin-electron transfer” relaxation mechanism was proposed to explain how the encaged Gd3+ ions of carbon nanohybrids interact with the surrounding water molecules. This approach opens new opportunities for developing highly efficient and low toxicity MRI contrast agents.

Polyhydroxylated fullerenols regulate macrophage for cancer adoptive immunotherapy and greatly inhibit the tumor metastasis

UNLABELLED Adoptive immunotherapy is a highly effective approach for cancer treatment. Several potential adoptive immunotherapies have high (though reversible) toxicities with disappointing results. Polyhydroxylated fullerenols have been demonstrated as promising antitumor drugs with low toxicities. In this study, we investigate whether polyhydroxylated fullerenols (C60(OH)22 and Gd@C82(OH)22) contribute to cancer immunotherapy by regulating macrophages. Our results show that fullerenols treatment enhances mitochondrial metabolism, phagocytosis and cytokine secretion. Moreover, activated macrophages inhibit the growth of several cancer cell types. It is likely that this inhibition is dependent on an NF-κB-mediated release of multiple cytokines. Using a lung metastasis model, we also show that autologous macrophages greatly suppress cancer cell metastasis to lung when they are activated by C60(OH)22 and Gd@C82(OH)22. More importantly, Gd@C82(OH)22 are shown to have stronger ability than C60(OH)22 to improve the macrophage function, which shed light on the rational design for nanomedicine and clinical application. FROM THE CLINICAL EDITOR The interest in the use of immunotherapy in cancer has rekindled recently. However, many approaches have shown disappointing results. In this study, the authors investigated the effects of polyhydroxylated fullerenol nanoparticles on regulating macrophages for immunotherapy. These positive findings may point a novel way to cancer treatment.

Enhanced performance of inverted organic photovoltaic cells using CNTs-TiOX nanocomposites as electron injection layer

In this study, we fabricated inverted organic photovoltaic cells with the structure ITO/carbon nanotubes (CNTs)-TiO(X)/P3HT:PCBM/MoO₃/Al by spin casting CNTs-TiO(X) nanocomposite (CNTs-TiO(X)) as the electron injection layer onto ITO/glass substrates. The power conversion efficiency (PCE) of the 0.1 wt% single-walled nanotubes (SWNTs)-TiO(X) nanocomposite device was almost doubled compared with the TiO(X) device, but with increasing concentration of the incorporated SWNTs in the TiO(X) film, the performance of the devices appeared to decrease rapidly. Devices with multi-walled NTs in the TiO(X) film have a similar trend. This phenomenon mainly depends on the inherent physical and chemical characteristics of CNTs such as their high surface area, their electron-accepting properties and their excellent carrier mobility. However, with increasing concentration of CNTs, CNTs-TiO(X) current leakage pathways emerged and also a recombination of charges at the interfaces. In addition, there was a significant discovery. The incorporated CNTs were highly conducive to enhancing the degree of crystallinity and the ordered arrangement of the P3HT in the active layers, due to the intermolecular π-π stacking interactions between CNTs and P3HT.

Quantification of carbon nanomaterials in vivo: direct stable isotope labeling on the skeleton of fullerene C-60

Concerns over the biosafety of carbon nanomaterials have been raised, due to their unique structure, properties and applications. However, a lack of easily accessible quantification methods for in vivo carbon nanomaterials largely limits the evaluation of their biosafety. Here, for the first time we adopted 13C stable isotopic labeling for the quantification of a fullerene in vivo. 13C-enriched fullerene C60 was synthesized by arc discharge and purified by high performance liquid chromatography. The 13C-enriched C60 was dispersed in tween 80 aqueous solution for animal administration and was then monitored and quantified by isotope ratio mass spectrometry after intravenous injection (i.v.). Our results showed that C60 quickly cleared from the blood circulation with a half-life of 14 min, and selective accumulation in the liver, spleen and lungs was observed, with slight decreases seen within 24 h. The pharmacokinetics of C60 could be evaluated using the two-compartmental model, in which the fast clearance after i.v. from the blood circulation and slow clearance by the uptake in tissues were revealed. The present findings demonstrated the feasibility of using 13C stable isotopically labeled carbon nanomaterials such as fullerene to trace and quantitatively monitor their bio-behavior in vivo, and suggested that 13C-enriched carbon nanomaterials might bring about a new platform to study the environmental fate of carbon nanomaterials.

Supercritical synthesis and characterization of SWNT-based one dimensional nanomaterials

The present study developed a novel, fast and efficient method to synthesize one dimensional nanotube-based materials via supercritical reactions and supercritical fluids. It was proved that supercritical organic fluids were good media to take materials into the nanocavity, not only as solvents but also as reaction agents. Different kinds of metals (Ni, Cu, Ag) and fullerenes (C(60), C(70), C(78), C(84), Gd@C(82), Er@C(82), Ho@C(82), Y@C(82)) were successfully inserted into nanotubes with small diameters by this technique, with various supercritical fluids such as C(2)H(5)OH, CH(3)OH or C(6)H(5)CH(3). The filling rates were proved to be more than 90%. The high filling efficiency and the properties of the as-generated materials were characterized by TEM, Raman, EDS and XPS. In principle, this technique can be applied to construct new types of nanomaterials, if we choose the appropriate supercritical reaction and fluid in the CNTs.