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Journal ArticleDOI

Computationally Guided Photothermal Tumor Therapy Using Long-Circulating Gold Nanorod Antennas

01 May 2009-Cancer Research (American Association for Cancer Research)-Vol. 69, Iss: 9, pp 3892-3900
TL;DR: An integrated approach to improved plasmonic therapy composed of multimodal nanomaterial optimization and computational irradiation protocol development is described and a single i.v. injection of PEG-NRs enabled destruction of all irradiated human xenograft tumors in mice.
Abstract: Plasmonic nanomaterials have the opportunity to considerably improve the specificity of cancer ablation by i.v. homing to tumors and acting as antennas for accepting externally applied energy. Here, we describe an integrated approach to improved plasmonic therapy composed of multimodal nanomaterial optimization and computational irradiation protocol development. We synthesized polyethylene glycol (PEG)-protected gold nanorods (NR) that exhibit superior spectral bandwidth, photothermal heat generation per gram of gold, and circulation half-life in vivo (t1/2, ~17 hours) compared with the prototypical tunable plasmonic particles, gold nanoshells, as well as ~2-fold higher X-ray absorption than a clinical iodine contrast agent. After intratumoral or i.v. administration, we fuse PEG-NR biodistribution data derived via noninvasive X-ray computed tomography or ex vivo spectrometry, respectively, with four-dimensional computational heat transport modeling to predict photothermal heating during irradiation. In computationally driven pilot therapeutic studies, we show that a single i.v. injection of PEG-NRs enabled destruction of all irradiated human xenograft tumors in mice. These studies highlight the potential of integrating computational therapy design with nanotherapeutic development for ultraselective tumor ablation.

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Citations
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Journal ArticleDOI
TL;DR: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘ how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?'
Abstract: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

3,335 citations

Journal ArticleDOI
TL;DR: It is argued that gold nanotechnology-enabled biomedicine is not simply an act of 'gilding the (nanomedicinal) lily', but that a new 'Golden Age' of biomedical nanotechnology is truly upon us.
Abstract: Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of ‘gilding the (nanomedicinal) lily’, but that a new ‘Golden Age’ of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references).

2,712 citations

Journal ArticleDOI
TL;DR: The history of the development of PEGylated nanoparticle formulations for systemic administration is described, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time.

2,465 citations


Cites background from "Computationally Guided Photothermal..."

  • ...“stealth” properties provided by surface PEG coatings [9, 36]....

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Journal ArticleDOI
TL;DR: This work is the first success of using carbon nanomaterials for efficient in vivo photothermal therapy by intravenous administration and suggests the great promise of graphene in biomedical applications, such as cancer treatment.
Abstract: Although biomedical applications of carbon nanotubes have been intensively studied in recent years, its sister, graphene, has been rarely explored in biomedicine. In this work, for the first time we study the in vivo behaviors of nanographene sheets (NGS) with polyethylene glycol (PEG) coating by a fluorescent labeling method. In vivo fluorescence imaging reveals surprisingly high tumor uptake of NGS in several xenograft tumor mouse models. Distinctive from PEGylated carbon nanotubes, PEGylated NGS shows several interesting in vivo behaviors including highly efficient tumor passive targeting and relatively low retention in reticuloendothelial systems. We then utilize the strong optical absorbance of NGS in the near-infrared (NIR) region for in vivo photothermal therapy, achieving ultraefficient tumor ablation after intravenous administration of NGS and low-power NIR laser irradiation on the tumor. Furthermore, no obvious side effect of PEGylated NGS is noted for the injected mice by histology, blood chemi...

2,151 citations

Journal ArticleDOI

1,989 citations

References
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Journal ArticleDOI
TL;DR: It is found that, after exposure to continuous red laser at 800 nm, malignant cells require about half the laser energy to be photothermally destroyed than the nonmalignant cells, so both efficient cancer cell diagnostics and selective photothermal therapy are realized at the same time.
Abstract: Due to strong electric fields at the surface, the absorption and scattering of electromagnetic radiation by noble metal nanoparticles are strongly enhanced. These unique properties provide the potential of designing novel optically active reagents for simultaneous molecular imaging and photothermal cancer therapy. It is desirable to use agents that are active in the near-infrared (NIR) region of the radiation spectrum to minimize the light extinction by intrinsic chromophores in native tissue. Gold nanorods with suitable aspect ratios (length divided by width) can absorb and scatter strongly in the NIR region (650−900 nm). In the present work, we provide an in vitro demonstration of gold nanorods as novel contrast agents for both molecular imaging and photothermal cancer therapy. Nanorods are synthesized and conjugated to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies and incubated in cell cultures with a nonmalignant epithelial cell line (HaCat) and two malignant oral epithelial ...

5,047 citations

Journal ArticleDOI
22 Aug 1997-Science
TL;DR: A highly selective, colorimetric polynucleotide detection method based on mercaptoalkyloligonucleotide-modified gold nanoparticle probes is reported, which can detect about 10 femtomoles of an oligonucleotide.
Abstract: A highly selective, colorimetric polynucleotide detection method based on mercaptoalkyloligonucleotide-modified gold nanoparticle probes is reported. Introduction of a single-stranded target oligonucleotide (30 bases) into a solution containing the appropriate probes resulted in the formation of a polymeric network of nanoparticles with a concomitant red-to-pinkish/purple color change. Hybridization was facilitated by freezing and thawing of the solutions, and the denaturation of these hybrid materials showed transition temperatures over a narrow range that allowed differentiation of a variety of imperfect targets. Transfer of the hybridization mixture to a reverse-phase silica plate resulted in a blue color upon drying that could be detected visually. The unoptimized system can detect about 10 femtomoles of an oligonucleotide.

4,334 citations


"Computationally Guided Photothermal..." refers background in this paper

  • ...The electromagnetic properties of plasmonic nanomaterials have been harnessed to develop ultrasensitive diagnostic (1, 2),...

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Journal ArticleDOI
TL;DR: While nanorods with a higher aspect ratio along with a smaller effective radius are the best photoabsorbing nanoparticles, the highest scattering contrast for imaging applications is obtained from nanorod of high aspect ratio with a larger effective radius.
Abstract: The selection of nanoparticles for achieving efficient contrast for biological and cell imaging applications, as well as for photothermal therapeutic applications, is based on the optical properties of the nanoparticles. We use Mie theory and discrete dipole approximation method to calculate absorption and scattering efficiencies and optical resonance wavelengths for three commonly used classes of nanoparticles: gold nanospheres, silica−gold nanoshells, and gold nanorods. The calculated spectra clearly reflect the well-known dependence of nanoparticle optical properties viz. the resonance wavelength, the extinction cross-section, and the ratio of scattering to absorption, on the nanoparticle dimensions. A systematic quantitative study of the various trends is presented. By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of extinction as well as the relative contribution of scattering to the extinction rapidly increases. Gold nanospheres in the size range commonly employed (∼40 nm)...

4,065 citations

Journal ArticleDOI
TL;DR: In vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage, and found good correlation with histological findings.
Abstract: Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.

3,774 citations


"Computationally Guided Photothermal..." refers background or methods in this paper

  • ...From a procedural perspective, despite a rich history of heat transfer modeling in the hyperthermia field, the use of quantitative modeling to predict the in vivo function of plasmonic nanomaterials has widely remained absent from their testing ( 5 , 6, 9, 11, 12)....

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  • ...To date, preparations of gold nanoshells and nanorods (NR) have shown considerable efficacy for tumor ablation using NIR light ( 5 , 6, 9, 10), with the most recent data showing complete resorption of f55% and f25% of irradiated tumors, respectively (11, 12)....

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  • ...Gold nanoshells (Nanocomposix) with 120 nm silica core and f15 nm gold shell were mixed with methyl-PEG-thiol as described ( 5 , 6, 9). Both PEGnanoshells and PEG-NRs were brought to 7 Ag Au/mL, as determined by inductively coupled plasma mass spectrometry (ICP-MS)....

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  • ...We show that PEG-NRs exhibit superior intrinsic absorption and photothermal efficacy compared with gold nanoshells (f6 times greater heat generation per weight gold), as well as substantially improved circulation times in vivo (f17 hours versus f4 hours), extrinsically imparted by their polymer coating ( 5 , 6). Surveying literature on inorganic nanoparticle circulation times in vivo, the circulation half-life of PEG-NRs is among the longest ......

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Journal Article
TL;DR: The surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition, are explored and the rational approaches in the design as well as the biological performance of such constructs are assessed.
Abstract: The rapid recognition of intravenously injected colloidal carriers, such as liposomes and polymeric nanospheres from the blood by Kupffer cells, has initiated a surge of development for "Kupffer cell-evading" or long-circulating particles. Such carriers have applications in vascular drug delivery and release, site-specific targeting (passive as well as active targeting), as well as transfusion medicine. In this article we have critically reviewed and assessed the rational approaches in the design as well as the biological performance of such constructs. For engineering and design of long-circulating carriers, we have taken a lead from nature. Here, we have explored the surface mechanisms, which affords red blood cells long-circulatory lives and the ability of specific microorganisms to evade macrophage recognition. Our analysis is then centered where such strategies have been translated and fabricated to design a wide range of particulate carriers (e.g., nanospheres, liposomes, micelles, oil-in-water emulsions) with prolonged circulation and/or target specificity. With regard to the targeting issues, attention is particularly focused on the importance of physiological barriers and disease states.

3,413 citations


"Computationally Guided Photothermal..." refers background in this paper

  • ...administration in mice to systemically target tumors through the enhanced permeability and retention effect (28)....

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  • ...Previously, polymer-stabilized inorganic nanomaterials have been described with circulation half-lives of a few hours in vivo (29, 30), including a variety of other gold nanoparticle preparations (22, 31–33), and on occasion with circulation times of f10 to 15 hours in mice (21, 28, 34)....

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  • ...models and clinical cancer treatment (28), the long circulation time reported here has the potential to directly translate to improved clinical tumor accumulation over previous nanoantennas....

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