Kurland et al., "Genomics and the Irreducible Nature of Eukaryote Cells" [abstract], doi:10.1126/science.1121674, p 1011-1014 v 312, Science, 19 May 2006.
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Ruoslahti . described self-amplifying tumor homing nanoparticles . The system was based on a CREKA peptide that not only recognizes clotted plasma proteins around tumor vessel walls or tumor stroma but also induces localized tumor clotting [-]. Fluorescein-labeled peptides, including the sulfhydryl group of the single cysteine residue, were coupled to amino dextran-coated iron oxide nanoparticles (CREKA-SPIO), and nanoparticles with at least 8,000 peptide molecules per particle were used for experiments. To reduce reticuloendothelial system (RES) uptake, a major obstacle to the homing of the nanoparticles, chelated Ni2+-liposome or liposomes as potential decoy particles were introduced prior to CREKA-SPIO injection. CREKA-SPIO treatment after pretreatment with the decoy particles displayed primary localization in the tumor vessels, and fewer particles were seen in the liver. The tumor-targeted nanoparticles were distributed along a meshwork in the clots, presumably formed by fibrin, suggesting that the nanoparticles infiltrated the depths of the clots. The tumor magnetization was quantitatively analyzed using a superconducting quantum interference device (SQUID), revealing that heparin injection prior to injection of CREKA-SPIO reduced the tumor accumulation of nanoparticles by >50% by eliminating intravascular clotting, although the treatment series did not considerably reduce the number of vessels. Thus, binding of CREKA-SPIO to tumor vessels did not require clotting activity, but intravascular clotting attracted more nanoparticles to the tumor, suggesting that tumor targeting was amplified.
The authors have declared that no conflict of interest exists.
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There is substantial concern that financial conflicts of interest on the part of investigators conducting clinical trials may compromise the well-being of research subjects.
Andromeda (TV Series 2000–2005) - IMDb
The broadened repertoire of RNA viruses suggests that colonization of land and growth in anatomical complexity in land plants coincided with the acquisition of novel sets of viruses with different strategies of infection and reproduction.
Created by Gene Roddenberry, Robert Hewitt Wolfe
In addition to organic coatings, core-shell structures, such as biocompatible silica- or gold-covered magnetic nanoparticles, have provided an attractive approach to developing stealth nanoparticles. Silica shells serve as protective stable nanoparticle coatings under aqueous conditions. The ability to encapsulate functional molecules within the nanoparticle matrix is a unique feature of these nanostructures. Hyeon and Moon developed Fe3O4 nanocrystal-embedded, core-shell mesoporous silica nanoparticles, and they demonstrated their multifunctional application to simultaneous MR/optical imaging and drug delivery . This study suggested a precise method for controlling the size of the silica nanoparticles smaller than 100 nm. The surfactant cetyltrimethylammonium bromide (CTAB) provided an organic template for the formation of a mesoporous silica shell and stabilized the hydrophobic Fe3O4 nanocrystals in an aqueous solution. The sol-gel process occurred through the template by using tetraethylorthosilicate (TEOS) and rhodamine B isothiocyanate (RITC)-labeled aminopropyltriethoxysilane (APS), and generated amine groups containing silica shell, to which PEG was covalently conjugated via succinimidyl end group to render further biocompatibility. Dox molecules loaded onto the as-synthesized Fe3O4@mSiO2(R)-PEG NPs to convey therapeutic properties. The core-shell structure exhibited magnetic and fluorescent properties, as well as a therapeutic index, suggesting the utility of the nanostructure in biomedical theranostic applications. On the other hand, gold provides several advantages as a coating material due to its inertness and its unique ability to absorb near-IR radiation. Hyeon and Cho described magnetic gold nanoshells (Mag-GNS) consisting of gold nanoshells encapsulating magnetic Fe3O4 nanoparticles as a novel nanomedical platform for simultaneous diagnostic imaging and thermal therapy . Monodisperse 7 nm Fe3O4 nanoparticles stabilized with 2-bromo-2-methylpropionic acid (BMPA) were covalently attached to amino-modified silica spheres through a direct nucleophilic substitution reaction between the bromo groups and the amino groups. Gold seed nanoparticles were then attached to the residual amino groups of the silica spheres. Finally, a complete 15 nm thick gold shell embedded with Fe3O4 nanoparticles formed around the silica spheres to generate Mag-GNS. To target breast cancer, an anti-HER2/neu antibody was conjugated onto the surfaces of the Mag-GNS. SKBR3 breast cancer cells treated with Mag-GNS could be detected using a clinical MRI system, followed by selective destruction by near-IR radiation.
With Kevin Sorbo, Lisa Ryder, Laura Bertram, Gordon Michael Woolvett
In general, nanoparticles tend to aggregate through hydrophobic interactions or attractive van der Waals forces in an effort to minimize the surface energy. In the blood stream, such aggregates can trigger opsonization, the process by which a particle becomes covered with opsonin proteins, thereby making it more visible to the mononuclear phagocytic system (MPS), such as RES. The phagocytic mechanisms render nanoparticles ineffective as theranostic devices by removing them from the bloodstream . Therefore, evading uptake by RES and increasing the blood circulation half-life are major challenges for developing theranostic nanoparticles in clinical applications . Several methods of camouflaging nanoparticles have been developed to yield 'stealth' nanoparticles, which are invisible to MPS. These approaches interfere with the binding of opsonin proteins to the nanoparticle surfaces in support of a long circulation half-life, thereby increasing the chance that the nanoparticles can effectively target tumor sites. In order to impart stealth properties to the nanoparticles, one of the most promising molecules is the FDA-approved PEG. Natural or synthetic polymers, small organic molecules, and core-shell structures have also been utilized for nanoparticle surface coatings. However, a high surface coverage can decrease binding to and uptake by target cancer cells. This section describes the use of several coating molecules as shielding materials. The optimal surface densities of the coating materials and the targeted ligands will be discussed.