Delivery of Targeted Nanoparticles Across the Blood-Brain Barrier Using a Detachable Targeting Ligand

Chronic diseases of the central nervous system are poorly treated due to the inability of most therapeutics to cross the blood-brain barrier. The blood-brain barrier is an anatomical and physiological barrier that severely restricts solute influx, including most drugs, from the blood to the brain. One promising method to overcome this obstacle is to use endogenous solute influx systems at the blood-brain barrier to transport drugs. Therapeutics designed to enter the brain through transcytosis by binding the transferrin receptor, however, are restricted within endothelial cells. The focus of this work was to develop a method to increase uptake of transferrin-containing nanoparticles into the brain by overcoming these restrictive processes.

To accomplish this goal, nanoparticles were prepared with surface transferrin molecules bound through various liable chemical bonds. These nanoparticles were designed to shed the targeting molecule during transcytosis to allow increased accumulation of nanoparticles within the brain.

Transferrin was added to the surface of nanoparticles through either redox or pH sensitive chemistry. First, nanoparticles with transferrin bound through disulfide bonds were prepared. These nanoparticles showed decreased avidity for the transferrin receptor after exposure to reducing agents and increased ability to enter the brain in vivo compared to those lacking the disulfide link.

Next, transferrin was attached through a chemical bond that cleaves at mildly acidic pH. Nanoparticles containing a cleavable link between transferrin and gold nanoparticle cores were found to both cross an in vitro model of the blood-brain barrier and accumulate within the brain in significantly higher numbers than similar nanoparticles lacking the cleavable bond. Also, this increased accumulation was not seen when using this same strategy with an antibody to transferrin receptor, indicating that behavior of nanoparticles at the blood-brain barrier varies depending on what type of targeting ligand is used.

Finally, polymeric nanoparticles loaded with dopamine and utilizing a superior acid-cleavable targeting chemistry were investigated as a potential treatment for Parkinson’s disease. These nanoparticles were capable of increasing dopamine quantities in the brains of healthy mice, highlighting the therapeutic potential of this design. Overall, this work describes a novel method to increase targeted nanoparticle accumulation in the brain.

Space-selective co-precipitation of silver and gold nanoparticles in femtosecond laser pulses irradiated Ag+, Au3+ co-doped silicate glass

We report on space-selective co-precipitation of silver and gold nanoparticles in Ag+, Au3+ co-doped silicate glasses by irradiation of femtosecond laser pulses and subsequent annealing at high temperatures. The color of the irradiated area in the glass sample changed from yellow to red with the increase of the annealing temperature. The effects of average laser power and annealing temperature on precipitation of the nanoparticles were investigated. A reasonable mechanism was proposed to explain the observed phenomena. (c) 2006 Elsevier Ltd. All rights reserved.

Effect of PbO on precipitation of laser-induced gold nanoparticles inside silicate glasses

We report on three-dimensional precipitation of Au nanoparticles in gold ions-doped silicate glasses by a femtosecond laser irradiation and further annealing. Experimental results show that PbO addition plays the double roles of inhibiting hole-trapped centers generation and promoting formation and growth of gold nanoparticles. Additionally, glass containing PbO shows an increased non-linear absorption after femtosecond laser irradiation and annealing. The observed phenomena are significant for applications such as fabrications of three-dimensional multi-colored images inside transparent materials and three-dimensional optical memory, and integrated micro-optical switches. (c) 2007 Elsevier B.V. All rights reserved.

Space-selective precipitation of Au nanoparticles inside silica gel

Au colloids were prepared by irradiation with a Nd:YAG laser. Au nanoparticles were characterized by absorption spectra, transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis. It is found that the wavelength of the laser has no effect on the size but the number of the Au nanoparticles. By irradiating a transparent silica gel doped with gold ions with the focused laser in the gel and subsequent exposing in air, a space-selective pattern of letter "P" consisting of Au nanoparticles was observed inside the silica gel.

Nanosecond nonlinear absorption in Au and Ag nanoparticles precipitated glasses induced by a femtosecond laser

We obtain Au and Ag nanoparticles precipitated in glasses by irradiation of focused femtosecond pulses, and investigate the nonlinear absorptions of the glasses by using Z-scan technique with ns pulses at 532 nm. We observe the saturable absorption behavior for An nanoparticles precipitated glasses and the reverse saturable ones for Ag ones. We also obtain, by fitting to the experimental results in the light of the local field effect near and away from the surface plasmon resonance, chi(m)((3)) = 4.5 x 10(-7) and 5.9 x 10(-8) esu for m the imaginary parts of the third-order susceptibilities for Au and Ag nanoparticles, respectively. The nonlinear response of Au nanoparticles in the glass samples arises mainly from the hot-electron contribution and the saturation of the interband transitions near the surface plasmon resonance, whereas that of Ag nanoparticles in the glass samples from the interband transitions. These show that the obtained glasses can be used as optoelectronic devices suiting for different demands. (c) 2005 Elsevier B.V. All rights reserved.

Precipitation of Ge nanoparticles from GeO2 glasses in transmission electron microscope

We show, using spatially resolved energy loss spectroscopy in a transmission electron microscopy (TEM), that GeO2 and GeO2-SiO2 glasses are extremely sensitive to high energy electrons. Ge nanoparticles can be precipitated in GeO2 glasses efficiently by the high-energy electron beam of a TEM. This is relevant to TEM characterization of luminescent Ge nanoparticles in silicate glasses, which may produce artificial results. (C) 2005 American Institute of Physics.

Preparation and optical properties of silicate glasses containing Pd nanoparticles

We report the space selective precipitation of Pd nanoparticles in Pd2+ -doped silicate glass by ultrashort laser pulses irradiation and further annealing. Absorption spectra, transmission electron microscopy, refractive index measurement and Z-scan technique demonstrated that metallic Pd nanoparticles were precipitated in the glass sample after irradiation by an 800-nm femtosecond laser and subsequent annealing at 600 degrees C. We discuss a refractive index change and nonlinear absorption that combines the precipitation of Pd nanoparticles. Crown Copyright (c) 2005 Published by Elsevier B.V. All rights reserved.

Absence of room-temperature ferromagnetism in Al-codoped Zn0.95Co0.05O nanoparticles

Nanocrystalline Zn0.95-xCo0.05AlxO (x=0, 0.01, 0.05) diluted magnetic semiconductors have been synthesized by an auto-combustion method. X-ray diffraction measurements indicated that Al-doped Zn0.95Co0.05O samples had the pure wurtzite structure. X-ray absorption spectroscopy, high-resolution transmission electron microscope, energy dispersive spectrometer and Co 2p core-level photoemission spectroscope analyses indicated that Co2+ substituted for Zn2+ without forming any secondary phases or impurities. Resistance measurements showed that the resistance values of Co and Al codoped samples were still so large in the giga magnitude. Magnetic investigations showed that nanocrystalline Al-doped Zn0.95Co0.05O samples had no indication of room temperature ferromagnetism. (C) 2007 Elsevier B.V. All rights reserved.