Biomedical applications of functionalized fullerene-based nanomaterials

Since their discovery in 1985, fullerenes have been investigated extensively due to their unique physical and chemical properties. In recent years, studies on functionalized fullerenes for various applications in the field of biomedical sciences have seen a significant increase. The ultimate goal is towards employing these functionalized fullerenes in the diagnosis and therapy of human diseases. Functionalized fullerenes are one of the many different classes of compounds that are currently being investigated in the rapidly emerging field of nanomedicine. In this review, the focus is on the three categories of drug delivery, reactive oxygen species quenching, and targeted imaging for which functionalized fullerenes have been studied in depth. In addition, an exhaustive list of the different classes of functionalized fullerenes along with their applications is provided. We will also discuss and summarize the unique approaches, mechanisms, advantages, and the aspect of toxicity behind utilizing functionalized fullerenes for biomedical applications

Self assembly of amphiphilic C60 fullerene derivatives into nanoscale supramolecular structures

<p>Abstract</p> <p>Background</p> <p>The amphiphilic fullerene monomer (AF-1) consists of a "buckyball" cage to which a Newkome-like dendrimer unit and five lipophilic C₁₂chains positioned octahedrally to the dendrimer unit are attached. In this study, we report a novel fullerene-based liposome termed 'buckysome' that is water soluble and forms stable spherical nanometer sized vesicles. Cryogenic electron microscopy (Cryo-EM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) studies were used to characterize the different supra-molecular structures readily formed from the fullerene monomers under varying pH, aqueous solvents, and preparative conditions.</p> <p>Results</p> <p>Electron microscopy results indicate the formation of bilayer membranes with a width of ~6.5 nm, consistent with previously reported molecular dynamics simulations. Cryo-EM indicates the formation of large (400 nm diameter) multilamellar, liposome-like vesicles and unilamellar vesicles in the size range of 50–150 nm diameter. In addition, complex networks of cylindrical, tube-like aggregates with varying lengths and packing densities were observed. Under controlled experimental conditions, high concentrations of spherical vesicles could be formed. <it>In vitro </it>results suggest that these supra-molecular structures impose little to no toxicity. Cytotoxicity of 10–200 μM buckysomes were assessed in various cell lines. Ongoing studies are aimed at understanding cellular internalization of these nanoparticle aggregates.</p> <p>Conclusion</p> <p>In this current study, we have designed a core platform based on a novel amphiphilic fullerene nanostructure, which readily assembles into supra-molecular structures. This delivery vector might provide promising features such as ease of preparation, long-term stability and controlled release.</p

New Insights into Metabolic Properties of Marine Bacteria Encoding Proteorhodopsins

Proteorhodopsin phototrophy was recently discovered in oceanic surface waters. In an effort to characterize uncultured proteorhodopsin-exploiting bacteria, large-insert bacterial artificial chromosome (BAC) libraries from the Mediterranean Sea and Red Sea were analyzed. Fifty-five BACs carried diverse proteorhodopsin genes, and we confirmed the function of five. We calculate that proteorhodopsin-exploiting bacteria account for 13% of microorganisms in the photic zone. We further show that some proteorhodopsin-containing bacteria possess a retinal biosynthetic pathway and a reverse sulfite reductase operon, employed by prokaryotes oxidizing sulfur compounds. Thus, these novel phototrophs are an unexpectedly large and metabolically diverse component of the marine microbial surface water

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Buckysomes: New Nanocarriers for Anticancer Drugs

Buckysomes, liposome-like vesicles comprised of dendritic C60 subunits that self-assemble into unilamellar vesicles, are unique nanovectors that have utility in drug delivery. We have prepared paclitaxel-embedded buckysomes (PEBs) and examined biodistriubition profiles with commercially available formulations of the drug. As compared to Abraxane, an albumin-bound formulation of paclitaxel, PEBs showed higher tissue accumulation in the liver and the kidney at 45 and 60 minutes and in the lungs at 30 minutes, making them suitable drug-delivery carriers for short-term therapy to the mentioned organs. These buckysomes can be further functionalized to specifically deliver paclitaxel to the tumor site

Self assembly of amphiphilic Cfullerene derivatives into nanoscale supramolecular structures-4

<p><b>Copyright information:</b></p><p>Taken from "Self assembly of amphiphilic Cfullerene derivatives into nanoscale supramolecular structures"</p><p>http://www.jnanobiotechnology.com/content/5/1/6</p><p>Journal of Nanobiotechnology 2007;5():6-6.</p><p>Published online 2 Aug 2007</p><p>PMCID:PMC2000908.</p><p></p>on. Kidney, Liver, and Macrophage cells exhibited little differences when compared to PBS controls after exposure to AF-1 at different concentrations and analyzed for membrane integrity (LDH) as well as cellular proliferation (MTT). Samples A, B, C, D and E are 2 mg/mL AF-1, 0.2 mg/mL AF-1, 0.02 mg/mL AF-1, cells only, and control respectively. Cells were treated with 0.1% HOfor negative control of MTT and 0.9% Triton X-100 for positive control of LDH

Self assembly of amphiphilic Cfullerene derivatives into nanoscale supramolecular structures-0

<p><b>Copyright information:</b></p><p>Taken from "Self assembly of amphiphilic Cfullerene derivatives into nanoscale supramolecular structures"</p><p>http://www.jnanobiotechnology.com/content/5/1/6</p><p>Journal of Nanobiotechnology 2007;5():6-6.</p><p>Published online 2 Aug 2007</p><p>PMCID:PMC2000908.</p><p></p>epared in 10 mM citrate at pH 7.0 and in (C) Buckysomes were prepared in 1 × PBS buffer at pH 7.15. The concentration of AF-1 was 2 mg/mL and preparations were made at room temperature. Images are representative of 20–30 different areas on the grid

Self assembly of amphiphilic Cfullerene derivatives into nanoscale supramolecular structures-5

<p><b>Copyright information:</b></p><p>Taken from "Self assembly of amphiphilic Cfullerene derivatives into nanoscale supramolecular structures"</p><p>http://www.jnanobiotechnology.com/content/5/1/6</p><p>Journal of Nanobiotechnology 2007;5():6-6.</p><p>Published online 2 Aug 2007</p><p>PMCID:PMC2000908.</p><p></p>on following several washes with PBS. Cells were fixed and counterstained with DAPI. (A) Superimposed image of fluorescein and DAPI emission. (B) Panel A superimposed with bright field image of cells. (C) Fluorescein emission at 520 nm. (D) DAPI emission at 461 nm. The scale bar for all panels is 50 μm