Fullerenol Nanoparticles with Structural Activity Induce Variable Intracellular Actin Filament Morphologies.

Fullerenol nanoparticles are promising for various biological applications; many studies have shown that they induce variable and diverse biological effects including side effects. Separation and purification of two fractions of fullerenols has demonstrated that they have varied chemical structures on the surfaces of their carbon cages. Actin is an important structural protein that is able to transform functional structures under varied physiological conditions. We assessed the abilities of the two fractions of fullerenols to attach to actin and induce variable morphological features in actin filament structures. Specifically the fullerenol fraction with a surface electric charge of -1.913 ± 0.008q (x10(-6) C) has percentages of C-OH and C=O on the carbon cage of 16.14 ± 0.60 and 17.55 ± 0.69. These features allow it to form intermolecular hydrogen bonds with actin at a stoichiometric ratio of four fullerenols per actin subunit. Molecular simulations revealed these specific binding sites and binding modes in atomic details in the interaction between the active fullerenol and actin filament. Conversely, these interactions were not possible for the other fraction of fullerenol with that percentages of C-OH and C=O on the carbon cage were 15.59 ± 0.01 and 1.94 ± 0.11. Neither sample induced appreciable cytotoxicity or acute cell death. After entering cells, active fullerenol binding to actin induces variable morphological features and may transform ATP-actin to ADP-actin. These changes facilitate the binding of ADF/cofilin, allowing cofilin to sever actin filaments to form cofilin/actin/fullerenol rods. Our findings suggest that fullerenol with structural activity binding disturbs actin filament structure, which may inhibit locomotion of cell or induce chronic side effects in to cells.

Synthesis of mesoporous Beta and Sn-Beta zeolites and their catalytic performances.

Mesoporous Beta zeolite has been successfully prepared through hydrothermal synthesis in the presence of cationic ammonium-modified chitosan as the meso-template. Through a subsequent solid-gas reaction between highly dealuminated mesoporous Beta zeolite and SnCl4 steam at an elevated temperature, mesoporous Sn-Beta has been facilely obtained. It was revealed that the addition of cationic chitosan induced the nanocrystal aggregation to particle sizes of ∼300 nm, giving rise to the intercrystalline/interparticle mesoporosity. In the Sn-implanting procedure, Sn species were demonstrated to be doped into the framework of the resulting mesoporous Beta zeolite in a tetrahedral environment without structural collapse. Due to the micro/mesoporous structures, both mesoporous Beta and Sn-Beta exhibited superior performances in α-pinene isomerization, Baeyer-Villiger oxidation of 2-adamantanone by hydrogen peroxide and the isomerization of glucose in water, respectively.

Toxicological properties of nanomaterials.

The development of engineered nanomaterials opens tremendous opportunities for their application as therapeutic and diagnostic tools, as well as in the fields of consumer products. As the newly developed material subtype, they exhibit great activities for the high ratio of surface to total atoms. In the bio-system, the activity can render nanomaterials some negative outcomes for their unexpected deposition in organs and cells, the cellular response to the exogenous substance and the interfacial reaction with biomolecules. In this review, we have discussed the evolution of nanotoxicology studies in the past ten years mainly emerging from our laboratory. The early in vivo studies mainly focused on the biokinetic of inhaled nanoparticles and their impacts on mammal tissues, such as the central nervous system, respiratory system, cardiovascular system and so on. Then the scope extended to engineered nanomaterials used as food additives and medicines, as well as their influence on alimentary and reproductive systems. In vitro experiments to study the nanoparticle-cell interaction and nanoparticle-biomolecule interplay are indispensable to reveal the mechanisms behind the macroscopic phenomenon. In addition, novel tools such as new model organisms and synchrotron radiation-based techniques are used to facilitate our understanding of the toxicology profile of nanomaterials.

Gd@C82(OH)22 nanoparticles constrain macrophages migration into tumor tissue to prevent metastasis.

Macrophages can be recruited to tumor tissues and play a supportive role in the invasion microenvironment. Since nanoparticles can be easily endocytosed by this kind of cell, the advances in nanotechnology offer a new sight to target macrophages in tumor tissues for diminishing harmful phenotypes. In the xenograft mouse model, we found that metallofullerol Gd@C82(OH)22 can not only reduced the macrophage density in the tumor tissue, but also decreased the expression of matrix metalloproteinase-9 produced by this kind of cell. To verify the phenomenon, a macrophage cell line, RAW264.7 was employed in the experiment, in vivo. Gd@C82(OH)22 nanoparticles can be engulfed by macrophages and the quantity was measured by inductively coupled plasma mass spectrometry. Fluorescent staining result showed that the particle induced the cells to adopt an elongated spindle morphology. The morphology alteration implied that the cells undergo mesenchymal migration, which is assisted by matrix metalloproteinase-9 to break down the extracellular matrix. But the reverse transcription PCR and western blots results indicated that the expression of matrix metalloproteinase-9 was reduced after the treatment of Gd@C82(OH)22. Thus, transwell migration assay indicated that macrophages were constrained to migrate through the collagen matrix.

Engineered design of theranostic upconversion nanoparticles for tri-modal upconversion luminescence/magnetic resonance/X-ray computed tomography imaging and targeted delivery of combined anticancer drugs.

Upconversion nanoparticles (UCNPs) are ideal building blocks for fabricating multifunctional theranostic agents for simultaneous diagnosis and therapy. We develop multifunctional nanoparticles based on NaGdF4:Yb/Er@NaGdF4 core-shell UCNPs, which are not only endowed with upconversion luminescence (UCL), magnetic resonance (MR) and X-ray computed tomography (CT) imaging ability, but also could be applied as nanocarriers for targeted drug delivery. We systematically investigate their upconversion luminescent, magnetic and X-ray attenuation properties. Importantly, for the first time, we report the controlled loading and delivery of a mixture of chemotherapeutic anticancer drugs, camptothecin (CPT) and doxorubicin (DOX), through UCNPs-based nanocarriers considering that the combined use of two or more drugs usually exhibits much better therapeutic efficacy than that of a single drug. By conjugating nanoparticles with folic acid (FA), which targets folate receptors over expressed on various types of cancer cells, we further demonstrate targeted tri-modal UCL/MR/CT cell imaging and drug delivery with UCNPs. Our results suggest the as-prepared nanocomposites are highly versatile and could potentially be used for simultaneous imaging and therapeutic applications.

Regulation on mechanical properties of collagen: enhanced bioactivities of metallofullerol.

Increased mechanical property of extracellular matrix (ECM) around tumor tissue is highly correlated to the progression of cancer, and now its efficient regulation is still a challenge. Here, we report that Gd@C82(OH)22-collagen composites greatly suppress the malignant progression of cancer cells in vitro, and the metallofullerol can efficiently reduce the mechanical property of collagen matrix. Further study indicates that Gd@C82(OH)22 can firmly bind to tropocollagen, facilitate the nuclei and microfibril formation. The interference to interactions among tropocollagens leads to decreased amount and disturbed structure of collagen fibers. C60(OH)24, the fullerol counterpart of Gd@C82(OH)22, is studied in parallel and their impacts on collagen are strikingly modest. The comparison data reveals that the enhanced bioactivity of Gd@C82(OH)22 is highly related with its surface-structure. This study is the first attempt to apply nanomedicines to manipulate the biophysical property of collagen matrix, providing a new sight to target ECM in cancer therapy. FROM THE CLINICAL EDITOR: Increased presence of "harder" collagen in the extracellular matrix (ECM) around the tumor tissue highly correlates with cancer progression. In this paper, a metallofullerol-based approach is reported as an efficient nanotechnology approach in reducing the mechanical properties of the synthesized collagen, paving the way to the development of novel anti-cancer therapies.

The effects of C60(C(COOH)2)2-FITC on proliferation and differentiation of human mesenchymal stem cells in vitro.

As manufactured nanoparticles, fullerene nanoparticles were used as the model to research the manufactured nanoparticles entering into cells and hence have been rapidly developed for biomedical uses. Human mesenchymal stem cells (hMSCs) have become the most widely used seeding cells in tissue engineering because they are readily obtained without ethical problems and are multipotent with regard to adipogenic, chondrogenic, and osteogenic lineages. Because of their favorable biological and cellular activities, C60 carboxyl derivatives are among the most widely studied C60 derivatives. FITC labeled C60(C(COOH)2)2 nanoparticles were charactered by FTIR, ESI-MS, XPS and DLS. The effects of C60(C(COOH)2)2-FITC on proliferation and differentiation of human mesenchymal stem cells (hMSCs) in vitro were observed. The fullerene nanoparticles are quickly internalized by the cells and they had low toxicity to proliferation of hMSCs. The C60(C(COOH)2)2 nanoparticles could promote cell proliferation, enhance osteoclast differentiation of hMSCs.

Adjusting the balance between effective loading and vector migration of macrophage vehicles to deliver nanoparticles.

The nature of macrophage allows the possibility that this cell type could be used as drug delivery system to track therapeutic drug nanoparticles (NPs) in cancer. However, there is no existing research on the regulation between effective loading of NPs and targeted delivery of macrophages. Here, we investigated the important parameters of intracellular NP quantity and the vector migration rate. Macrophage loading capacity was obtained by comparing the uptake quantity of varisized NPs, and the delivery ability of loaded cells was determined by measuring vector migration rates. We observed a positive correlation between the size of NPs and directed macrophage migration. Our findings suggest that the molecular mechanism of migration vector rate regulation involved increased expression levels of colony-stimulating factor-1 (CSF-1) receptor and integrin induced by 100-nm and 500-nm particles. The ability of macrophages uptake to varisized NPs showed the opposite trend, with the increased vector rate of cell migration influenced by NPs. We are able to demonstrate the important balance between effective macrophage loading and targeted delivery. By adjusting the balance parameters, it will be possible to utilize NPs in macrophage-mediated disease diagnosis and therapy.

A simple route to synthesize mesoporous ZSM-5 templated by ammonium-modified chitosan.

Uniform mesoporous zeolite ZSM-5 crystals have been successfully fabricated through a simple hydrothermal synthetic method by utilizing ammonium-modified chitosan and tetrapropylammonium hydroxide (TPAOH) as the meso- and microscale template, respectively. It was revealed that mesopores with diameters of 5-20 nm coexisted with microporous network within mesoporous ZSM-5 crystals. Ammonium-modified chitosan was demonstrated to serve as a mesoporogen, self-assembling with the zeolite precursor through strong static interactions. As expected, the prepared mesoporous ZSM-5 exhibited greatly enhanced catalytic activities compared with conventional ZSM-5 and Al-MCM-41 in reactions involving bulky molecules, such as the Claisen-Schmidt condensation of 2-hydroxyacetophenone with benzaldehyde and the esterification reaction of dodecanoic acid and 2-ethylhexanol.