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ABSTRACT: Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients.
Nanoscale 05/2012; 4(12):3776-80. · 5.91 Impact Factor
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ABSTRACT: Gold nanorods manifest a readily tunable longitudinal plasmon resonance with light and consequently have potential for use
in photothermal therapeutics. Recent work by others has shown how gold nanoshells and rods can be used to target cancer cells,
which can then be destroyed using relatively high power laser radiation (∼1×105 to 1×1010W/m2). Here we extend this concept to demonstrate how gold nanorods can be modified to bind to target macrophage cells, and show
that high intensity laser radiation is not necessary, with even 5×102W/m2 being sufficient, provided that a total fluence of ∼30J/cm2 is delivered. We used the murine cell line RAW 264.7 and the monoclonal antibody CD11b, raised against murine macrophages,
as our model system and a 5mW solid state diode laser as our energy source. Exposure of the cells labeled with gold nanorods
to a laser fluence of 30J/cm2 resulted in 81% cell death compared to only 0.9% in the control, non-labeled cells.
Journal of Nanoparticle Research 04/2012; 9(6):1109-1124. · 3.29 Impact Factor
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ABSTRACT: A poly(ethylene glycol) (PEG)-modified dendritic poly(l-lysine) (PEG-WeKG6) containing tryptophan residues in its core was synthesized as an oligonucleotide carrier to tumors after systemic injection. PEG-WeKG6 formed a stable complex with double-stranded deoxyoligonucleotide (ODN). The size and the zeta-potential of the complex were smaller than those of a dendritic poly(l-lysine) without PEG (WeKG6). To study the biodistribution of the complexes in tumor-bearing mice after intravenous injection, the dendrimers and the oligonucleotide were labeled with gadolinium and Cy5, respectively. Our results show that PEG modification of the dendrimer improved the stability of ODN in blood circulation. Effective accumulation of the PEG-WeKG6/ODN complex in the tumor tissue was found 24 h after the injection. These results indicate that PEG-WeKG6 is suitable for forming a complex with any genetic or therapeutic material for efficient delivery to tumors.
Journal of Biomaterials Science Polymer Edition 01/2012; · 1.69 Impact Factor
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Small 01/2011; 7(2):215-20. · 8.35 Impact Factor
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ABSTRACT: Gold nanoparticles have unique optical properties such as surface-plasmon and photothermal effects. Such properties have resulted in gold nanoparticles having several clinical applications. Gold nanorods (which are rod-shaped gold nanoparticles) show a surface plasmon band in the near-infrared region. They have therefore been proposed as contrast agents for bioimaging, or as heating devices for photothermal therapy. Polyethylene glycol-modified gold nanorods systemically administrated into mice can be detected with integrating sphere, and the stability of the gold nanorods in blood flow evaluated. After intravenous injection of gold nanorods followed by near-infrared laser irradiation, significant tumor damage triggered by the photothermal effect was observed. To deliver gold nanorods to the target tissue, thermosensitive polymer gel-coated gold nanorods were prepared. After intravenous injection of the gel-modified gold nanorods and irradiation of the tumor, a larger amount of gold was detected in the irradiated tumor than in the non-irradiated tumor. This effect is due to the hydrophobic interaction between the cellular membrane or the extracellular matrix and the gel surfaces induced by the photothermal effect. Furthermore, the photothermal effect enhanced the permeability of the stratum corneum of the skin. As a result of treatment of the skin with ovalbumin and gold nanorods followed by near-infrared light irradiation, a significant amount of protein was detected in the skin. The gold nanorods therefore showed several functions as a photothermal nanodevice for bioimaging, thermal therapy, and a drug delivery system.
Yakugaku zasshi journal of the Pharmaceutical Society of Japan 12/2010; 130(12):1671-7. · 0.39 Impact Factor
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ABSTRACT: The increasing number of bacterial strains that are resistant to available pharmaceutical compounds is a vital issue for public health. Innovative approaches will be required to improve the methods for both diagnosis and destruction of these organisms. Here, we consider the possible role that can be played by technologies based on gold nanoparticles. Gold nanoparticles generally are considered to be biologically inert but can be engineered to possess chemical or photothermal functionality. A growing body of research is devoted to the potential use of these nanoparticles in the diagnosis and treatment of bacterial infections. The results are both promising and intriguing, and suggest a range of new strategies to identify, target or destroy pathogenic organisms.
Trends in Biotechnology 04/2010; 28(4):207-13. · 9.15 Impact Factor
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ABSTRACT: The RAFT technique has been increasingly used to generate polymers for potential biological applications. However, to-date, the toxicity of the RAFT-polymers has received limited attention. In this study, the in vitro cytotoxicity of three different, RAFT-synthesized, water-soluble polymers was investigated using three different adherent cell lines via CellTiter-Blue cell viability and the cytosolic enzyme lactate dehydrogenase (LDH) cytotoxicity assays. In brief, P(OEG-A) and P(OEG-MA) samples bearing omega-dithiobenzoate or omega-trithiocarbonate end groups and varying P(HPMA) samples bearing omega-dithiobenzoate, omega-trithiocarbonate, or non-RAFT end groups, were investigated using Chinese hamster ovary cells (CHO-K1), mouse macrophage cells (Raw264.7), and mouse fibroblast cells (NIH3T3). Any changes in the morphology of the cells after treatment with polymers were monitored via microscopy. The cytotoxicity of the polymers after treatment with metabolic liver enzymes was also evaluated. The average viability of CHO-K1 and NIH3T3 cells treated with dithiobenzoate- and trithiocarbonate-ended OEG-based polymers (1000 microM) for 24 h was close to 100%. The RAW264.7 cells were slightly more sensitive when incubated with dithiobenzoate-ended polymers (cell viability above 73%) for 24 h. The viability of the cells after 3 days of incubation with the polymers either slightly decreased or showed no change with respect to the viabilities obtained after 1 day of incubation. Analyses of cell morphology and cell membrane integrity via microscopy and a LDH assay confirmed the cell viability results obtained via CellTiter-Blue Assay. Unexpectedly, dithiobenzoate-ended P(HPMA) (at 1000 microM) exhibited high cytotoxicity after 24 h with all three cells lines. Further investigation of various P(HPMA) samples revealed that trithiocarbonate-ended and HPMA-capped P(HPMA)s at the same concentration were nontoxic over the same period of time. Also, dithiobenzoate-ended P(HPMA) at low concentrations (< or = 200 microM) can be tolerated by the cells tested.
Biomacromolecules 02/2010; 11(2):412-20. · 5.48 Impact Factor
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ABSTRACT: The unique optical, chemical, and biological properties of gold nanoparticles have resulted in them becoming of clinical interest in several applications including drug and gene delivery. The attractive features of gold nanoparticles include their surface plasmon resonance, the controlled manner in which they interact with thiol groups, and their non-toxic nature. These attributes can be exploited to provide an effective and selective platform to obtain a targeted intracellular release of some substance. The use of gold nanoparticles can also increase the stability of the payload. Here we review recent advances in the use of gold nanoparticles in drug and gene delivery systems. The topics of surface modification, site-specificity and drugs and gene and gene delivery are discussed.
Journal of Controlled Release 12/2009; 149(1):65-71. · 5.73 Impact Factor
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Small 04/2009; 5(9):1030-4. · 8.35 Impact Factor
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ABSTRACT: Conjugates of gold nanoparticles and antibodies have useful functionalities. Here, we show how they can be used to selectively target and destroy parasitic protozoans. Gold nanorods were conjugated with an anti-Toxoplasma gondii antibody and used to target the extracellular tachyzoite which is an infectious form of an obligate parasite Toxoplasma gondii. Subsequent laser irradiation was used to kill the targeted protozoans. This concept provides a new paradigm for the treatment of parasitic protozoans.
Nano Letters 01/2008; 7(12):3808-12. · 13.20 Impact Factor
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ABSTRACT: Rod-shaped gold nanoparticles ('nanorods') have recently attracted widespread attention due to their unique optical properties and facile synthesis. In particular, they can support a longitudinal surface plasmon, which results in suspensions of them having a strong extinction peak in the upper visible or near-infrared parts of the spectrum. The position of this peak can be readily tuned by controlling the shape of the rods. In addition, the surface of the nanorods can be functionalized by a very wide variety of molecules. This has led to interest in their use as selective biomarkers in biodiagnostics or for selective targeting in photothermal thearapeutics. Here, we review the recent advances in the use of gold nanorods in these applications. Additionally, the information available regarding their biocompatibility is discussed.
Biotechnology & genetic engineering reviews 01/2008; 25:93-112. · 0.50 Impact Factor
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ABSTRACT: Nanoparticles of gold, which are in the size range 10-100 nm, undergo a plasmon resonance with light. This is a process whereby the electrons of the gold resonate in response to incoming radiation causing them to both absorb and scatter light. This effect can be harnessed to either destroy tissue by local heating or release payload molecules of therapeutic importance. Gold nanoparticles can also be conjugated to biologically active moieties, providing possibilities for targeting to particular tissues. Here, we review the progress made in the exploitation of the plasmon resonance of gold nanoparticles in photo-thermal therapeutic medicine.
Trends in Biotechnology 03/2006; 24(2):62-7. · 9.15 Impact Factor
