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.
Antioxidant Single-Walled Carbon Nanotubes Lucente-Schultz, Rebecca M; Moore, Valerie C; Leonard, Ashley D ...
Journal of the American Chemical Society,
03/2009, Letnik:
131, Številka:
11
Journal Article
Recenzirano
Single-walled carbon nanotubes (SWCNTs) and ultrashort SWCNTs (US-SWCNTs) were functionalized with derivatives of the phenolic antioxidant, butylated hydroxytoluene (BHT). By using the oxygen radical ...absorbance capacity (ORAC) assay, the oxygen radical scavenging ability of the SWCNT antioxidants is nearly 40 times greater than that of the radioprotective dendritic fullerene, DF-1. In addition, ORAC results revealed two divergent trends in the antioxidant potential of SWCNTs, depending on the type of functionalization employed. When existing pendant sites on US-SWCNTs were further functionalized by either covalent or noncovalent interactions of the existing pendant sites with a BHT derivative, the amount of BHT-derivative loading proportionately increased the overall antioxidant activity. If, however, functionalization occurred via covalent functionalization of a BHT-derivative directly to the SWCNT sidewall, the amount of BHT-derivative loading was inversely proportional to the overall antioxidant activity. Therefore, increasing the number of pendant sites on the SWCNT sidewalls by covalent functionalization led to a concomitant reduction in ORAC activity, suggesting that the nanotube itself is a better radical scavenger than the BHT-derivatized SWCNT. Cytotoxicity assays showed that both nonfunctionalized and BHT-derivatized SWCNTs have little or no deleterious effect on cell viability. Therefore, SWCNTs may be attractive agents for antioxidant materials and medical therapeutics research.
After exposure to an agonist, platelets are activated and become aggregated. They also shed membrane microparticles that participate in the pathogenesis of thrombosis, hyper-coagulation and ...inflammation. However, microvesiculation can potentially disrupt the integrity of platelet aggregation by shedding the membrane receptors and phosphatidylserine critical for forming and stabilising a platelet clot. We tested the hypothesis that adhesion and microvesiculation are functions of different subsets of platelets at the time of haemostasis by real-time monitoring of agonist-induced morphological changes and microvesiculation of human platelets.We identified two types of platelets that are adherent to fibrinogen: a high density bubble shape (HDBS) and low-density spread shape (LDSS). Adenosine diphosphate (ADP) predominantly induced HDBS platelets to vesiculate, whereas LDSS platelets were highly resistant to such vesiculation. Thrombin-receptor activating peptide (TRAP) stabilised platelets against microvesiculation by promoting a rapid HDBS-to-LDSS morphological transition. These activities of ADP and TRAP were reversed for platelets in suspension, independent of an engagement integrin αIIbβ3. As the result of membrane contact, LDSS platelets inhibited the microvesiculation of HDBS platelets in response to ADP. Aspirin and clopidogrel inhibited ADP-induced microvesiculation through different mechanisms. These results suggest that platelet aggregation and microvesiculation occur in different subsets of platelets and are differently regulated by agonists, platelet-platelets and platelet-fibrinogen interactions.
We report the preparation and preliminary in vitro studies of nanocarriers termed “buckysomes,” which are self-assembled, spherical nanostructures composed of the amphiphilic fullerene AF-1. By ...inducing AF-1 self-assembly at an elevated temperature of 70 °C, dense spherical buckysomes with diameters of 100−200 nm were formed, as observed by electron microscopy and dynamic light scattering. The amphiphilic nature of AF-1 results in the formation of many hydrophobic regions within the buckysomes, making them ideal for embedding hydrophobic molecules to be tested in a drug delivery scheme. After confirming the cellular internalization of buckysomes embedded with the hydrophobic fluorescent dye 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate, we embedded paclitaxel, a highly hydrophobic anticancer drug. The in vitro therapeutic efficacy of the paclitaxel-embedded buckysomes toward suppression of MCF-7 breast cancer cell growth was compared to that of Abraxane, a commercially available, nanoparticle-albumin-bound formulation of paclitaxel. Notably, the paclitaxel-embedded buckysomes demonstrated a similar efficacy to that observed with Abraxane in cell viability studies; these results were confirmed microscopically. Moreover, negative control studies of MCF-7 viability using empty buckysomes demonstrated that the buckysomes were not cytotoxic. The results of our studies suggest that buckysomes prepared from self-assembly of AF-1 at 70 °C are promising nanomaterials for the delivery of hydrophobic molecules.
The realization that blood‐borne delivery systems must overcome a multiplicity of biological barriers has led to the fabrication of a multistage delivery system (MDS) designed to temporally release ...successive stages of particles or agents to conquer sequential barriers, with the goal of enhancing delivery of therapeutic and diagnostic agents to the target site. In its simplest form, the MDS comprises stage‐one porous silicon microparticles that function as carriers of second‐stage nanoparticles. Cellular uptake of nontargeted discoidal silicon microparticles by macrophages is confirmed by electron and atomic force microscopy (AFM). Using superparamagnetic iron oxide nanoparticles (SPIONs) as a model of secondary nanoparticles, successful loading of the porous matrix of silicon microparticles is achieved, and retention of the nanoparticles is enhanced by aminosilylation of the loaded microparticles with 3‐aminopropyltriethoxysilane. The impact of silane concentration and reaction time on the nature of the silane polymer on porous silicon is investigated by AFM and X‐ray photoelectron microscopy. Tissue samples from mice intravenously administered the MDS support co‐localization of silicon microparticles and SPIONs across various tissues with enhanced SPION release in spleen, compared to liver and lungs, and enhanced retention of SPIONs following silane capping of the MDS. Phantom models of the SPION‐loaded MDS display negative contrast in magnetic resonance images. In addition to forming a cap over the silicon pores, the silane polymer provides free amines for antibody conjugation to the microparticles, with both VEGFR‐2‐ and PECAM‐specific antibodies leading to enhanced endothelial association. This study demonstrates the assembly and cellular association of a multiparticle delivery system that is biomolecularly targeted and has potential for applications in biological imaging.
The retention of superparamagnetic iron oxide nanoparticles (SPIONs) in a porous silicon matrix is enhanced by aminosilylation of the loaded matrix with 3‐aminopropyltriethoxysilane. Cellular uptake of the drug‐delivery system and release of nanoparticles from the porous matrix are demonstrated.
The construction and electrochemical characterization of electrodes with submicrometer dimensions (2 nm < r app < 1000 nm) is reported. Electrodes are prepared by insulating etched Pt wires with ...electrophoretic paint, as recently reported by Slevin et al. (Electrochem. Commun. 1999, 1, 282). The voltammetric behavior of these electrodes was evaluated using nine different redox systems; well-defined and stable diffusion-limited responses were obtained in all but two cases. The behavior of these electrodes was investigated in aqueous ferrocenylmethyltrimethylammonium (FcTMA+) solutions in the presence and absence of excess supporting electrolyte to determine the influence of diffusion and migration on molecular transport in the nanometer spatial regime. Our findings indicate that the voltammetric behavior of these electrodes can be described using classical transport theory for r app > 10 nm.
Abstract Herein we report a novel vesicle-forming iodinated contrast agent for applications in computed tomographic (CT) imaging and drug delivery. Specifically, we have chemically modified a ...phosphatidylcholine lipid that is commonly used in liposome formation to create an iodinated lipid that self-assembles into ~50-150 nm iodoliposomes possessing as-prepared imaging contrast functionality. These iodoliposomes are structurally organized such that the iodinated moieties are contained within the vesicle's bilayer, leaving the liposomal interior unoccupied and thus available for encapsulating drugs. The iodoliposomes were characterized using electron microscopy and dynamic light scattering. We also calculated the iodoliposomes' iodine encapsulation efficiency, which was sufficient for use in current CT imaging protocols. These iodinated liposomes could also serve as multifunctional carriers upon the encapsulation of pharmaceutical agents, permitting simultaneous CT imaging and therapeutic treatment. Alternatively, the commercially available iodinated contrast agent iohexol could be encapsulated inside the iodoliposomes' aqueous core to further enchance their imaging contrast.
The amphiphilic fullerene monomer (AF-1) consists of a "buckyball" cage to which a Newkome-like dendrimer unit and five lipophilic C12 chains 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.
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. In vitro results suggest that these supra-molecular structures impose little to no toxicity. Cytotoxicity of 10-200 muM buckysomes were assessed in various cell lines. Ongoing studies are aimed at understanding cellular internalization of these nanoparticle aggregates.
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.
We evaluated the specific binding of anti-intercellular adhesion molecule 1 (ICAM-1) conjugated liposomes (immunoliposomes, or ILs) to activated human coronary artery endothelial cells (HCAEC) with ...the purpose of designing a computed tomographic imaging agent for early detection of atherosclerotic plaques. Covalent attachment of anti-ICAM-1 monoclonal antibodies to pre-formed liposomes stabilized with polyethylene glycol yielded ILs, with a coupling efficiency of the ICAM-1 to the liposomes of 10% to 24%. The anti-ICAM-1-labeled ILs had an average diameter of 136 nm as determined by dynamic light-scattering and cryogenic electron microscopy. The ILs' encapsulation of 5-N-acetyl-(2,3-dihydroxypropyl)-amino)-N, N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-benzene-1,3-dicarboxamide (iohexol) was determined to be 18% to 19% by a dialysis technique coupled with ultraviolet detection of free iohexol. This encapsulation corresponded to 30 to 38 mg iodine per mL IL solution, and the ILs exhibited 91% to 98.5% iohexol retention at room temperature and under physiologic conditions. The specific binding of the ILs to cultured, activated HCAEC was measured using flow cytometry, enzyme-linked immunosorbent assays, and fluorescence microscopy. The immunosorbent assays demonstrated the specificity of binding of anti-ICAM-1 to ICAM-1 compared with control studies using nonspecific immunoglobulin G-labeled ILs. Flow cytometry and fluorescence microscopy experiments demonstrated the expression of ICAM-1 on the surface of activated HCAEC. Therefore, our iohexol-filled ILs demonstrated potential for implementation in computed tomographic angiography to noninvasively detect atherosclerotic plaques that are prone to rupture.
Pristine, individualized single-walled carbon nanotubes (SWCNTs) have been noncovalently captured within PEG-terminated block copolymer amphiphiles. Two cross-linkable amphiphiles were evaluated: ...polyethylene glycol-polyacrylic acid-polystyrene (PEG-PAA-PS) and polyethylene glycol-polybutadiene (PEG-PB). The resulting self-assembled PEG-PAA-PS structures, called PEG-eggs, are freely soluble in water and stable in physiological media. SWCNTs in PEG-eggs retain their intrinsic near-infrared fluorescence, resist exchange with serum proteins, and are non-cytotoxic to mouse macrophage and human renal cells based on
in vitro viability assays.
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