TY - Generic T1 - Toxicities and antitumor efficacy of tumor-targeted AuNRs in mouse model T2 - CANCER RESEARCH Y1 - 2013 A1 - Peng, Xianghong A1 - Mackey, Megan A1 - Austin, Lauren A1 - Oyelere, Adegboyega A1 - Chen, Georgia A1 - Huang, Xiaohua A1 - El-Sayed, Mostafa A. A1 - Shin, Dong M JA - CANCER RESEARCH PB - AMER ASSOC CANCER RESEARCH 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA VL - 73 SN - 0008-5472 J1 - Cancer Res. ER - TY - CHAP T1 - Applications of gold nanorods for cancer imaging and photothermal therapy T2 - Methods in Molecular Biology Y1 - 2010 A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A A1 - Grobmyer, SR KW - cancer KW - gold nanorods KW - imaging KW - photothermal therapy AB - This chapter describes the application of gold nanorods in biomedical imaging and photothermal therapy. The photothermal properties of gold nanorods are summarized and the synthesis as well as antibody conjugation of gold nanorods is outlined. Biomedical applications of gold nanorods include cancer imaging using their enhanced scattering properties and photothermal therapy using their enhanced nonradioactive photothermal property. JA - Methods in Molecular Biology PB - Springer VL - 624 SN - 1064-3745 UR - http://dx.doi.org/10.1007/978-1-60761-609-2_23 M3 - 10.1007/978-1-60761-609-2_23 ER - TY - JOUR T1 - Comparative study of photothermolysis of cancer cells with nuclear-targeted or cytoplasm-targeted gold nanospheres: continuous wave or pulsed lasers JF - Journal of Biomedical Optics Y1 - 2010 A1 - Huang, Xiaohua A1 - Kang, Bin A1 - Qian, Wei A1 - Mackey, M. A. A1 - Chen, P. C. A1 - Oyelere, A. K. A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A AB - We conduct a comparative study on the efficiency and cell death pathways of continuous wave (cw) and nanosecond pulsed laser photothermal cancer therapy using gold nanospheres delivered to either the cytoplasm or nucleus of cancer cells. Cytoplasm localization is achieved using arginine-glycine-aspartate peptide modified gold nanospheres, which target integrin receptors on the cell surface and are subsequently internalized by the cells. Nuclear delivery is achieved by conjugating the gold nanospheres with nuclear localization sequence peptides originating from the simian virus. Photothermal experiments show that cell death can be induced with a single pulse of a nanosecond laser more efficiently than with a cw laser. When the cw laser is applied, gold nanospheres localized in the cytoplasm are more effective in inducing cell destruction than gold nanospheres localized at the nucleus. The opposite effect is observed when the nanosecond pulsed laser is used, suggesting that plasmonic field enhancement of the nonlinear absorption processes occurs at high localization of gold nanospheres at the nucleus. Cell death pathways are further investigated via a standard apoptosis kit to show that the cell death mechanisms depend on the type of laser used. While the cw laser induces cell death via apoptosis, the nanosecond pulsed laser leads to cell necrosis. These studies add mechanistic insight to gold nanoparticle-based photothermal therapy of cancer. (c) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3486538] VL - 15 SN - 1083-3668 N1 - Huang, Xiaohua Kang, Bin Qian, Wei Mackey, Megan A. Chen, Po C. Oyelere, Adegboyega K. El-Sayed, Ivan H. El-Sayed, Mostafa A. M3 - 10.1117/1.3486538 ER - TY - JOUR T1 - Dark-field light scattering imaging of living cancer cell component from birth through division using bioconjugated gold nanoprobes JF - Journal of Biomedical Optics Y1 - 2010 A1 - Qian, Wei A1 - Huang, Xiaohua A1 - Kang, Bin A1 - El-Sayed, Mostafa A AB - Novel methods and technologies that could extend and complement the capabilities of the prevailing fluorescence microscope in following the cell cycle under different perturbations are highly desirable in the area of biological and biomedical imaging. We report a newly designed instrument for long-term light scattering live cell imaging based on integrating a homebuilt environmental cell incubation minichamber and an angled dark-field illumination system into a conventional inverted light microscope. Peptide-conjugated gold nanoparticles that are selectively delivered to either the cytoplasmic or nuclear region of the cell are used as light scattering contrast agents. The new system enables us to carry out continuous and intermittence-free dark-field live cell imaging over several tens of hours. A variety of applications of this imaging system are demonstrated, such as monitoring the nuclear uptake of peptide-conjugated gold nanoparticles, tracking the full cycle of cancer cells from birth to division, following the chromosome dynamics during cell mitosis, and observing the intracellular distribution of gold nanoparticles after cell division. We also discuss the overall effect of nuclear targeting gold nanoparticles on the cell viability of parent and daughter cells. VL - 15 UR - http://dx.doi.org/10.1117/1.3477179 M3 - 10.1117/1.3477179 ER - TY - CHAP T1 - Fluorescent Quenching Gold Nanoparticles: Potential Biomedical Applications T2 - Metal Enhanced Fluorescence Y1 - 2010 A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A KW - biomedical applications KW - fluorescent quenching KW - gold nanoparticles KW - Raman spectroscopy KW - surface plasmon resonance JA - Metal Enhanced Fluorescence PB - Wiley Online Library UR - http://dx.doi.org/10.1002/9780470642795.ch20 M3 - 10.1002/9780470642795.ch20 ER - TY - JOUR T1 - A Reexamination of Active and Passive Tumor Targeting by Using Rod-Shaped Gold Nanocrystals and Covalently Conjugated Peptide Ligands JF - ACS Nano Y1 - 2010 A1 - Huang, Xiaohua A1 - Peng, Xianghong A1 - Wang, Yiqing A1 - Wang, Yuxiang A1 - Shin, Dong M A1 - El-Sayed, Mostafa A A1 - Nie, Shuming AB - The targeted delivery of nanoparticles to solid tumors is one of the most important and challenging problems in cancer nanomedicine, but the detailed delivery mechanisms and design principles are still not well understood. Here we report quantitative tumor uptake studies for a class of elongated gold nanocrystals (called nanorods) that are covalently conjugated to tumor-targeting peptides. A major advantage in using gold as a ?tracer? is that the accumulated gold in tumors and other organs can be quantitatively determined by elemental mass spectrometry (gold is not a natural element found in animals). Thus, colloidal gold nanorods are stabilized with a layer of polyethylene glycols (PEGs) and are conjugated to three different ligands: (i) a single-chain variable fragment (ScFv) peptide that recognizes the epidermal growth factor receptor (EGFR); (ii) an amino terminal fragment (ATF) peptide that recognizes the urokinase plasminogen activator receptor (uPAR); and (iii) a cyclic RGD peptide that recognizes the av?3 integrin receptor. Quantitative pharmacokinetic and biodistribution data show that these targeting ligands only marginally improve the total gold accumulation in xenograft tumor models in comparison with nontargeted controls, but their use could greatly alter the intracellular and extracellular nanoparticle distributions. When the gold nanorods are administered via intravenous injection, we also find that active molecular targeting of the tumor microenvironments (e.g., fibroblasts, macrophages, and vasculatures) does not significantly influence the tumor nanoparticle uptake. These results suggest that for photothermal cancer therapy, the preferred route of gold nanorod administration is intratumoral injection instead of intravenous injection.The targeted delivery of nanoparticles to solid tumors is one of the most important and challenging problems in cancer nanomedicine, but the detailed delivery mechanisms and design principles are still not well understood. Here we report quantitative tumor uptake studies for a class of elongated gold nanocrystals (called nanorods) that are covalently conjugated to tumor-targeting peptides. A major advantage in using gold as a ?tracer? is that the accumulated gold in tumors and other organs can be quantitatively determined by elemental mass spectrometry (gold is not a natural element found in animals). Thus, colloidal gold nanorods are stabilized with a layer of polyethylene glycols (PEGs) and are conjugated to three different ligands: (i) a single-chain variable fragment (ScFv) peptide that recognizes the epidermal growth factor receptor (EGFR); (ii) an amino terminal fragment (ATF) peptide that recognizes the urokinase plasminogen activator receptor (uPAR); and (iii) a cyclic RGD peptide that recognizes the av?3 integrin receptor. Quantitative pharmacokinetic and biodistribution data show that these targeting ligands only marginally improve the total gold accumulation in xenograft tumor models in comparison with nontargeted controls, but their use could greatly alter the intracellular and extracellular nanoparticle distributions. When the gold nanorods are administered via intravenous injection, we also find that active molecular targeting of the tumor microenvironments (e.g., fibroblasts, macrophages, and vasculatures) does not significantly influence the tumor nanoparticle uptake. These results suggest that for photothermal cancer therapy, the preferred route of gold nanorod administration is intratumoral injection instead of intravenous injection. PB - American Chemical Society VL - 4 SN - 1936-0851 UR - http://dx.doi.org/10.1021/nn102055s CP - 10 N1 - doi: 10.1021/nn102055s J1 - ACS Nano ER - TY - JOUR T1 - Gold Nanoparticles Surface Plasmon Field Effects on the Proton Pump Process of the Bacteriorhodopsin Photosynthesis JF - Journal of the American Chemical Society Y1 - 2009 A1 - Biesso, A. A1 - Qian, Wei A1 - Huang, Xiaohua A1 - El-Sayed, Mostafa A AB - The rate of the proton pump of bacteriorhodopsin photosynthetic system is examined in the presence of a gold nanorod plasmon field. It is found that while the rate of the proton dissociation from the protonated Schiff base is not affected, the rate of its reprotonation increases. These results are qualitatively discussed in terms of several possible mechanisms. VL - 131 SN - 0002-7863 N1 - Biesso, Arianna Qian, Wei Huang, Xiaohua El-Sayed, Mostafa A. M3 - 10.1021/ja8088873 ER - TY - JOUR T1 - Gold Nanorods: From Synthesis and Properties to Biological and Biomedical Applications JF - Advanced Materials Y1 - 2009 A1 - Huang, Xiaohua A1 - Neretina, Svetlana A1 - El-Sayed, Mostafa A AB - Noble metal nanoparticles; are capable of confining resonant photons in such a manner as to induce coherent surface plasmon oscillation of their conduction band electrons, a phenomenon leading to two important properties. Firstly, the confinement of the photon to the nanoparticle's dimensions leads to a large increase in its electromagnetic field and consequently great enhancement of all the nanoparticle's radiative properties, such as absorption and scattering. Moreover, by confining the photon's wavelength to the nanoparticle's small dimensions, there exists enhanced imaging resolving powers, which extend well below the diffraction limit, a property of considerable importance in potential device applications. Secondly, the strongly absorbed light by the nanoparticles is followed by a rapid dephasing of the coherent electron motion in tandem with an equally rapid energy transfer to the lattice, a process integral to the technologically relevant photothermal properties of plasmonic nanoparticles. Of all the possible nanoparticle shapes, gold nanorods are especially intriguing as they offer strong plasmonic fields while exhibiting excellent tunability and biocompatibility. We begin this review of gold nanorods by summarizing their radiative and nonradiative properties. Their various synthetic methods are then outlined with an emphasis on the seed-mediated chemical growth. In particular, we describe nanorod spontaneous self-assembly, chemically driven assembly, and polymer-based alignment. The final section details current studies aimed at applications in the biological and biomedical fields. VL - 21 SN - 0935-9648 N1 - Huang, Xiaohuo Neretina, Svetiana El-Sayed, Mostafa A. M3 - 10.1002/adma.200802789 ER - TY - JOUR T1 - Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice JF - Cancer Letters Y1 - 2008 A1 - Dickerson, E. B. A1 - Dreaden, Erik A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - Chu, H. H. A1 - Pushpanketh, S. A1 - McDonald, J. F. A1 - El-Sayed, Mostafa A AB - Plasmonic photothermal therapy (PPTT) is a minimally-invasive oncological treatment strategy in which photon energy is selectively administered and converted into heat sufficient to induce cellular hyperthermia. The present work demonstrates the feasibility of in vivo PPTT treatment of deep-tissue malignancies using easily-prepared plasmonic gold nanorods and a small, portable, inexpensive near-infrared (NIR) laser. Dramatic size decreases in squamous cell carcinoma xenografts were observed for direct (P < 0.0001) and intravenous (P < 0.0008) administration of pegylated gold nanorods in nu/nu mice. Inhibition of average tumor growth for both delivery methods was observed over a 13-day period, with resorption of >57% of the directly-injected tumors and 25% of the intravenously-treated tumors. Published by Elsevier Ltd. VL - 269 SN - 0304-3835 N1 - Dickerson, Erin B. Dreaden, Erik C. Huang, Xiaohua El-Sayed, Ivan H. Chu, Hunghao Pushpanketh, Sujatha McDonald, John F. El-Sayed, Mostafa A. M3 - 10.1016/j.canlet.2008.04.026 ER - TY - JOUR T1 - Noble Metals on the Nanoscale: Optical and Photothermal Properties and Some Applications in Imaging, Sensing, Biology, and Medicine JF - Accounts of Chemical Research Y1 - 2008 A1 - Jain, Prashant K A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A AB - Noble metal nanostructures attract much interest because of their unique properties, including large optical field enhancements resulting in the strong scattering and absorption of light. The enhancement in the optical and photothermal properties of noble metal nanoparticles arises from resonant oscillation of their free electrons in the presence of light, also known as localized surface plasmon resonance (LSPR). The plasmon resonance can either radiate light (Mie scattering), a process that finds great utility in optical and imaging fields, or be rapidly converted to heat (absorption); the latter mechanism of dissipation has opened up applications in several new areas. The ability to integrate metal nanoparticles into biological Systems has had greatest impact in biology and biomedicine. In this Account we discuss the plasmonic properties of gold and silver nanostructures and present examples of how they are being utilized for biodiagnostics, biophysical studies, and medical therapy. For instance, taking advantage of the strong LSPR scattering of gold nanoparticles conjugated with specific targeting molecules allows the mollecule-specific imaging and diagnosis of diseases such as cancer. We emphasize in particular how the unique tunability of the plasmon resonance properties of metal nanopartides through variation of their size, shape, composition, and medium allows chemists to design nanostructures geared for specific bio-applications. We discuss some interesting nanostructure geometries, including nanorods, nanoshells, and nanopartide pairs, that exhibit dramatically enhanced and tunable plasmon resonances, making them highly suitable for bio-applications. Tuning the nanostructure shape (e.g., nanoprisms, nanorods, or nanoshells) is another means of enhancing the sensitivity of the LSPR to the nanopartide environment and, thereby, designing effective biosensing agents. Metal nanopartide pairs or assemblies display distance-dependent plasmon resonances as a result of field coupling. A universal scaling model, relating the plasmon resonance frequency to the interpartide distance in terms of the particle size, becomes potentially useful for measuring nanoscale distances (and their changes) in biological systems. The strong plasmon absorption and photothermal conversion of gold nanoparticles has been exploited in cancer therapy through the selective localized photothermal heating of cancer cells. For nanorods or nanoshells, the LSPR can be tuned to the near-infrared region, making it possible to perform in vivo imaging and therapy. The examples of the applicators of noble metal nanostructures provided herein can be readily generalized to other areas of biology and medicine because plasmonic nanomaterials exhibit great range, versatility, and systematic tunability of their optical attributes. VL - 41 SN - 0001-4842 N1 - Jain, Prashant K. Huang, Xiaohua El-Sayed, Ivan H. El-Sayed, Mostafa A. M3 - 10.1021/ar7002804 ER - TY - JOUR T1 - Plasmonic photothermal therapy (PPTT) using gold nanoparticles JF - Lasers in Medical Science Y1 - 2008 A1 - Huang, Xiaohua A1 - Jain, Prashant K A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A. KW - display AB - The use of lasers, over the past few decades, has emerged to be highly promising for cancer therapy modalities, most commonly the photothermal therapy method, which employs light absorbing dyes for achieving the photothermal damage of tumors, and the photodynamic therapy, which employs chemical photosensitizers that generate singlet oxygen that is capable of tumor destruction. However, recent advances in the field of nanoscience have seen the emergence of noble metal nanostructures with unique photophysical properties, well suited for applications in cancer phototherapy. Noble metal nanoparticles, on account of the phenomenon of surface plasmon resonance, possess strongly enhanced visible and near-infrared light absorption, several orders of magnitude more intense compared to conventional laser phototherapy agents. The use of plasmonic nanoparticles as highly enhanced photoabsorbing agents has thus introduced a much more selective and efficient cancer therapy strategy, viz. plasmonic photothermal therapy (PPTT). The synthetic tunability of the optothermal properties and the bio-targeting abilities of the plasmonic gold nanostructures make the PPTT method furthermore promising. In this review, we discuss the development of the PPTT method with special emphasis on the recent in vitro and in vivo success using gold nanospheres coupled with visible lasers and gold nanorods and silica-gold nanoshells coupled with near-infrared lasers. VL - 23 SN - 0268-8921 N1 - Huang, Xiaohua Jain, Prashant K. El-Sayed, Ivan H. El-Sayed, Mostafa A. M3 - 10.1007/s10103-007-0470-x ER - TY - JOUR T1 - Cancer cells assemble and align gold nanorods conjugated to antibodies to produce highly enhanced, sharp, and polarized surface Raman spectra: A potential cancer diagnostic marker JF - Nano Letters Y1 - 2007 A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - Qian, Wei A1 - El-Sayed, Mostafa A AB - Human oral cancer cells are found to assemble and align gold nanorods conjugated to anti-epidermal growth factor receptor (anti-EGFR) antibodies. Immnoconjugated gold nanorods and nanospheres were shown previously to exhibit strong Rayleigh (Mie) scattering useful for imaging. In the present letter, molecules near the nanorods on the cancer cells are found to give a Raman spectrum that is greatly enhanced (due to the high surface plasmon field of the nanorod assembly in which their extended surface plasmon fields overlap), sharp (due to a homogeneous environment), and polarized (due to anisotropic alignments). These observed properties can be used as diagnostic signatures for cancer cells. VL - 7 SN - 1530-6984 N1 - Huang, Xiaohua El-Sayed, Ivan H. Qian, Wei El-Sayed, Mostafa A. M3 - 10.1021/nl070472c ER - TY - JOUR T1 - Effect of plasmonic gold nanoparticles on benign and malignant cellular autofluorescence: A novel probe for fluorescence based detection of cancer JF - Technology in Cancer Research & Treatment Y1 - 2007 A1 - El Sayed, I.H. A1 - Huang, Xiaohua A1 - Macheret, F. A1 - Humstoe, J. O. A1 - Kramer, R. A1 - El-Sayed, Mostafa A AB - Due to the strong surface fields of noble metal nanoparticles, absorption and scattering of electromagnetic radiation is greatly enhanced. Noble metallic nanoparticles represent potential novel optical probes for simultaneous molecular imaging and photothermal cancer therapy using the enhanced scattering and absorption of light. Further, gold nanoparticles can affect molecular fluorescence via chemical, electronic, or photonic interactions. Live cells generate fluorescence due to intracellular and extracellular molecules. Differences in the biochemical composition between healthy and malignant cells can be exploited in vivo to help identify cancer spectroscopically. The interaction of gold nanoparticles with cellular autofluorescence has not yet been characterized. We hypothesized that gold nanoparticles delivered to live cells in vitro would alter cellular autofluorescence and may be useful as a novel class of contrast agent for fluorescence based detection of cancer. The fluorescence of two fluorophores that are responsible for tissue autofluorescence, NADH and collagen, and of two oral squamous carcinoma cell lines and one immortalized benign epithelial cell line were measured in vitro. Gold nanoparticles of different shapes, both spheres and rods, quenched the fluorescence of the soluble NADH and collagen. Reduction of NADH fluorescence was due to oxidation of NADH to NAD+ catalyzed by gold nanoparticles (results we previously published). Reduction of collagen fluorescence appears due to photonic absorption of light. Furthermore, a mean quenching of 12/8% (p < 0.00050) of the tissue autofluorescence of cell suspensions was achieved in this model when nanospheres were incubated with the live cells. Gold nanospheres significantly decrease cellular autofluorescence of live cells under physiological conditions when excited at 280nm. This is the first report to our knowledge to suggest the potential of developing targeted gold nanoparticles optical probes as contrast agents for fluorescence based diagnoses of cancer. VL - 6 SN - 1533-0346 N1 - El-Sayed, Ivan Huang, Xiaohua Macheret, Fima Humstoe, Joseph Oren Kramer, Randall El-Sayed, Mostafa ER - TY - JOUR T1 - Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostic and therapy JF - Nanomedicine Y1 - 2007 A1 - Huang, Xiaohua A1 - Jain, Prashant K A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A AB - Recent years have seen tremendous progress in the design and study of nanomaterials geared towards biological and biomedical applications, most notable among these being the noble metal nanoparticles. In this review, we outline the surface-plasmon resonance-enhanced optical properties of colloidal gold nanoparticles directed towards recent biomedical applications with an emphasis on cancer diagnostics and therapeutics. Methods of molecular-specific diagnostics/detection of cancer, including strongly enhanced surface plasmon resonance light-scattering, surface-enhanced emission of gold nanorods and surf ace-enhanced Raman scattering, are described. We also discuss the plasmonic photothermal therapy of cancer achieved by using the strongly enhanced surface-plasmon resonance absorption of gold nanospheres and nanorods. VL - 2 SN - 1743-5889 N1 - Huang, Xiaohua Jain, Prashant K. El-Sayed, Ivan H. El-Sayed, Mostafa A. M3 - 10.2217/17435889.2.5.681 ER - TY - JOUR T1 - Peptide-conjugated gold nanorods for nuclear targeting JF - Bioconjugate Chemistry Y1 - 2007 A1 - Oyelere, A. K. A1 - Chen, P. C. A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A AB - Resonant electron oscillations on the surface of noble metal nanoparticles (Au, Ag, Cu) create the surface plasmon resonance (SPR) that greatly enhances the absorption and Rayleigh (Mie) scattering of light by these particles. By adjusting the size and shape of the particles from spheres to rods, the SPR absorption and scattering can be tuned from the visible to the near-infrared region (NIR) where biologic tissues are relatively transparent. Further, gold nanorods greatly enhance surface Raman scattering of adsorbed molecules. These unique properties make gold nanorods especially attractive as optical sensors for biological and medical applications. In the present work, gold nanorods are covalently conjugated with a nuclear localization signal peptide through a thioalkyl-triazole linker and incubated with an immortalized benign epithelial cell line and an oral cancer cell line. Dark field light SPR scattering images demonstrate that nanorods are located in both the cytoplasm and nucleus of both cell lines. Single cell micro-Raman spectra reveal enhanced Raman bands of the peptide as well as molecules in the cytoplasm and the nucleus. Further, the Raman spectra reveal a difference between benign and cancer cell lines. This work represents an important step toward both imaging and Raman-based intracellular biosensing with covalently linked ligand-nanorod probes. VL - 18 SN - 1043-1802 N1 - Oyelere, Adegboyega K. Chen, Po C. Huang, Xiaohua El-Sayed, Ivan H. El-Sayed, Mostafa A. M3 - 10.1021/bc070132i ER - TY - JOUR T1 - The potential use of the enhanced nonlinear properties of gold nanospheres in photothermal cancer therapy JF - Lasers in Surgery and Medicine Y1 - 2007 A1 - Huang, Xiaohua A1 - Qian, Wei A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A AB - Background and Objective: Laser photothermal therapy (PTT) is practiced at the moment using short laser pulses. The use of plasmonic nanoparticles as contrast agents can decrease the laser energy by using the optical property of the nanoparticles and improve the tumor selectivity by the molecular probes on the particle surface. In this study, we aim at selective and efficient PTT by exploiting the nonlinear optical properties of aggregated spherical gold nanoparticles conjugated to anti-epidermal growth factor receptor (anti-EGFR) antibodies using short NIR laser pulses. Study Design/Materials and Methods: Spherical gold nanoparticles are synthesized and conjugated to anti-EGFR antibodies to specifically target HSC oral cancer cells. The nanoparticles are characterized by micro-absorption spectra and dark field light scattering imaging. Photothermal destructions of control and nanoparticle treated cancer cells are carried out with a ferntosecond Ti:Sapphire laser at 800 nm with a pulse duration of 100 femtoseconds and repetition rate of 1 kHz. Results: The laser power threshold for the photothermal destruction of cells after the nanoparticle treatment is found to be 20 times lower than that required to destroy the cells in the normal PTT, that is, without nanoparticles. The number of destroyed cells is quadratically dependent on the laser power. The number of dead cells shows a nonlinear dependence on the concentration of gold nanoparticles that are specifically targeted to cancer cells. Conclusions: The energy threshold and selectivity of PTT can greatly benefit from the use of the plasmonic enhanced nonlinear optical processes of spherical gold nanoparticles conjugated to anti-EGFR antibodies. The quadratic dependence of the photothermal efficiency on the pulsed NIR laser power indicates a second harmonic generation or a two photon absorption process. The observed nonlinear dependence on the gold nanoparticle concentration suggests that aggregated nanospheres are responsible for the observed enhanced photothermal destruction of the cells. VL - 39 SN - 0196-8092 N1 - Huang, Xiaohua Qian, Wei El-Sayed, Ivan H. El-Sayed, Mostafa A. M3 - 10.1002/lsm.20577 ER - TY - JOUR T1 - Review of some interesting surface plasmon resonance-enhanced properties of noble metal nanoparticles and their applications to biosystems JF - Plasmonics Y1 - 2007 A1 - Jain, Prashant K A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A AB - Noble metal, especially gold (Au) and silver (Ag) nanoparticles exhibit unique and tunable optical properties on account of their surface plasmon resonance (SPR). In this review, we discuss the SPR-enhanced optical properties of noble metal nanoparticles, with an emphasis on the recent advances in the utility of these plasmonic properties in molecular-specific imaging and sensing, photo-diagnostics, and selective photothermal therapy. The strongly enhanced SPR scattering from Au nanoparticles makes them useful as bright optical tags for molecular-specific biological imaging and detection using simple dark-field optical microscopy. On the other hand, the SPR absorption of the nanoparticles has allowed their use in the selective laser photothermal therapy of cancer. We also discuss the sensitivity of the nanoparticle SPR frequency to the local medium dielectric constant, which has been successfully exploited for the optical sensing of chemical and biological analytes. Plasmon coupling between metal nanoparticle pairs is also discussed, which forms the basis for nanoparticle assembly-based biodiagnostics and the plasmon ruler for dynamic measurement of nanoscale distances in biological systems. PB - Springer VL - 2 SN - 1557-1955 UR - http://dx.doi.org/10.1007/s11468-007-9031-1 CP - 3 M3 - 10.1007/s11468-007-9031-1 ER - TY - JOUR T1 - Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods JF - Journal of the American Chemical Society Y1 - 2006 A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - Qian, Wei A1 - El-Sayed, Mostafa A. KW - display AB - 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 cell lines (HOC 313 clone 8 and HSC 3). The anti-EGFR anti body-conjugated nanorods bind specifically to the surface of the malignant-type cells with a much higher affinity due to the overexpressed EGFR on the cytoplasmic membrane of the malignant cells. As a result of the strongly scattered red light from gold nanorods in dark field, observed using a laboratory microscope, the malignant cells are clearly visualized and diagnosed from the nonmalignant cells. 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. Thus, both efficient cancer cell diagnostics and selective photothermal therapy are realized at the same time. VL - 128 SN - 0002-7863 N1 - Huang, XH El-Sayed, IH Qian, W El-Sayed, MA M3 - 10.1021/ja057254a ER - TY - JOUR T1 - Determination of the minimum temperature required for selective photothermal destruction of cancer cells with the use of immunotargeted gold nanoparticles JF - Photochemistry and Photobiology Y1 - 2006 A1 - Huang, Xiaohua A1 - Jain, Prashant K A1 - El Sayed, I.H. A1 - El-Sayed, Mostafa A AB - Laser photothermal therapy of cancer with the use of gold nanoparticles immunotargeted to molecular markers on the cell surface has been shown to be an effective modality to selectively kill cancer cells at much lower laser powers than those needed for healthy cells. To elucidate the minimum light dosimetry required to induce cell death, photothermal destruction of two cancerous cell lines and a noncancerous cell line treated with antiepidermal growth factor receptor (anti-EGFR) anti body-conjugated gold nanoparticles is studied, and a numerical heat transport model is used to estimate the local temperature rise within the cells as a result of the laser heating of the gold nanoparticles. It is found that cell samples with higher nanoparticle loading require a lower incident laser power to achieve a certain temperature rise. Numerically estimated temperatures of 70-80 degrees C achieved by heating the gold particles agree well with the measured threshold temperature for destruction of the cell lines by oven heating and those measured in an earlier nanoshell method. Specific binding of anti-EGFR antibody to cancerous cells overexpressing EGFR selectively increases the gold nanoparticle loading within cancerous cells, thus allowing the cancerous cells to be destroyed at lower laser power thresholds than needed for the noncancerous cells. In addition, photothermal therapy using gold nanoparticles requires lower laser power thresholds than therapies using conventional dyes due to the much higher absorption coefficient of the gold nanoparticles. VL - 82 SN - 0031-8655 N1 - Huang, XH Jain, PK El-Sayed, IH El-Sayed, MA M3 - 10.1562/2005-12-14-ra-754 ER - TY - JOUR T1 - Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles JF - Cancer Letters Y1 - 2006 A1 - El Sayed, I.H. A1 - Huang, Xiaohua A1 - El-Sayed, Mostafa A AB - Efficient conversion of strongly absorbed light by plasmonic gold nanoparticles to heat energy and their easy bioconjugation suggest their use as selective photothermal agents in molecular cancer cell targeting. Two oral squamous carcinoma cell lines (HSC 313 and HOC 3 Clone 8) and one benign epithelial cell line (HaCaT) were incubated with anti-epithelial growth factor receptor (EGFR) antibody conjugated gold nanoparticles and then exposed to continuous visible argon ion laser at 514 nm. It is found that the malignant cells require less than half the laser energy to be killed than the benign cells after incubation with anti-EGFR antibody conjugated Au nanoparticles. No photothermal destruction is observed for all types of cells in the absence of nanoparticles at four times energy required to kill the malignant cells with anti-EGFR/Au conjugates bonded. An nanoparticles thus offer a novel class of selective photothermal agents using a CW laser at low powers. The potential of using this selective technique in molecularly targeted photothermal therapy in vivo is discussed (c) 2005 Elsevier Ireland Ltd. All rights reserved. VL - 239 SN - 0304-3835 N1 - El-Sayed, Ivan H. Huang, Xiaohua El-Sayed, Mostafa A. M3 - 10.1016/j.canlet.2005.07.035 ER - TY - JOUR T1 - Gold nanoparticles: Catalyst for the oxidation of NADH to NAD(+) JF - Journal of Photochemistry and Photobiology B-Biology Y1 - 2005 A1 - Huang, Xiaohua A1 - El Sayed, I.H. A1 - Yi, X. B. A1 - El-Sayed, Mostafa A AB - Nicotinamide adenine dinucleotide is an important coenzyme involved in the production of ATP, the fuel of energy, in every cell. It alternates between the oxidized form NAD(+) and the reduced form dihydronicotinamide adenine dinucleotide (NADH) and serves as a hydrogen and electron carrier in the cellular respiratory processes. In the present work, the catalytic effect of gold nanoparticles on the oxidization of NADH to NAD(+) was investigated. The addition of gold nanoparticles was found to quench the NADH fluorescence intensities but had no effect on the fluorescence lifetime. This suggested that the fluorescence quenching was not due to coupling with the excited state, but due to changing the ground state of NADH. The intensity of the 340 nm absorption band of NADH was found to decrease while that of the 260 nm band of NAD+ was found to increase as the concentration of gold nanoparticles increased. This conversion reaction was further supported by nuclear magnetic resonance and mass spectroscopy. The effect of the addition of NADH was found to slightly red shift and increase the intensity of the surface plasmon absorption band of gold nanoparticles at 520 nm. This gives a strong support that the conversion of NADH to NAD(+) is occurring on the surface of the gold nanoparticles, i.e. NADH is surface catalyzed by the gold nanoparticles. The catalytic property of this important reaction might have important future applications in biological and medical fields. (c) 2005 Elsevier B.V. All rights reserved. VL - 81 SN - 1011-1344 N1 - Huang, XH El-Sayed, IH Yi, XB El-Sayed, MA M3 - 10.1016/j.jphotobiol.2005.05.010 ER - TY - JOUR T1 - Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: Applications in oral cancer JF - Nano Letters Y1 - 2005 A1 - El Sayed, I.H. A1 - Huang, Xiaohua A1 - El-Sayed, Mostafa A. KW - display AB - Gold nanoparticles with unique optical properties may be useful as biosensors in living whole cells. Using a simple and inexpensive technique, we recorded surface plasmon resonance (SPR) scattering images and SPR absorption spectra from both colloidal gold nanoparticles and from gold nanoparticles conjugated to monoclonal anti-epidermal growth factor receptor (anti-EGFR) antibodies after incubation in cell cultures with a nonmalignant epithelial cell line (HaCaT) and two malignant oral epithelial cell lines (HOC 313 clone 8 and HSC 3). Colloidal gold nanoparticles are found in dispersed and aggregated forms within the cell cytoplasm and provide anatomic labeling information, but their uptake is nonspecific for malignant cells. The anti-EGFR antibody conjugated nanoparticles specifically and homogeneously bind to the surface of the cancer type cells with 600% greater affinity than to the noncancerous cells. This specific and homogeneous binding is found to give a relatively sharper SPR absorption band with a red shifted maximum compared to that observed when added to the noncancerous cells. These results suggest that SPR scattering imaging or SPR absorption spectroscopy generated from antibody conjugated gold nanoparticles can be useful in molecular biosensor techniques for the diagnosis and investigation of oral epithelial living cancer cells in vivo and in vitro. VL - 5 SN - 1530-6984 N1 - El-Sayed, IH Huang, XH El-Sayed, MA M3 - 10.1021/nl050074e ER -