@inbook {809,
	title = {Applications of gold nanorods for cancer imaging and photothermal therapy},
	booktitle = {Methods in Molecular Biology},
	volume = {624},
	year = {2010},
	pages = {343-357},
	publisher = {Springer},
	organization = {Springer},
	chapter = {23},
	abstract = {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.},
	keywords = {cancer, gold nanorods, imaging, photothermal therapy},
	isbn = {1064-3745},
	doi = {10.1007/978-1-60761-609-2_23},
	url = {http://dx.doi.org/10.1007/978-1-60761-609-2_23},
	author = {Huang, Xiaohua and El Sayed, I.H. and El-Sayed, Mostafa A and Grobmyer, SR}
}
@article {1097,
	title = {Comparative study of photothermolysis of cancer cells with nuclear-targeted or cytoplasm-targeted gold nanospheres: continuous wave or pulsed lasers},
	journal = {Journal of Biomedical Optics},
	volume = {15},
	number = {5},
	year = {2010},
	note = {Huang, Xiaohua Kang, Bin Qian, Wei Mackey, Megan A. Chen, Po C. Oyelere, Adegboyega K. El-Sayed, Ivan H. El-Sayed, Mostafa A.},
	month = {Sep-Oct},
	abstract = {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]},
	isbn = {1083-3668},
	doi = {10.1117/1.3486538},
	author = {Huang, Xiaohua and Kang, Bin and Qian, Wei and Mackey, M. A. and Chen, P. C. and Oyelere, A. K. and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@inbook {816,
	title = {Fluorescent Quenching Gold Nanoparticles: Potential Biomedical Applications},
	booktitle = {Metal Enhanced Fluorescence},
	year = {2010},
	month = {06/2010},
	pages = {573-599},
	publisher = {Wiley Online Library},
	organization = {Wiley Online Library},
	chapter = {20},
	keywords = {biomedical applications, fluorescent quenching, gold nanoparticles, Raman spectroscopy, surface plasmon resonance},
	doi = {10.1002/9780470642795.ch20},
	url = {http://dx.doi.org/10.1002/9780470642795.ch20},
	author = {Huang, Xiaohua and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1131,
	title = {Gold nanorod assisted near-infrared plasmonic photothermal therapy (PPTT) of squamous cell carcinoma in mice},
	journal = {Cancer Letters},
	volume = {269},
	number = {1},
	year = {2008},
	note = {Dickerson, Erin B. Dreaden, Erik C. Huang, Xiaohua El-Sayed, Ivan H. Chu, Hunghao Pushpanketh, Sujatha McDonald, John F. El-Sayed, Mostafa A.},
	month = {Sep},
	pages = {57-66},
	abstract = {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.},
	isbn = {0304-3835},
	doi = {10.1016/j.canlet.2008.04.026},
	author = {Dickerson, E. B. and Dreaden, Erik and Huang, Xiaohua and El Sayed, I.H. and Chu, H. H. and Pushpanketh, S. and McDonald, J. F. and El-Sayed, Mostafa A}
}
@article {1124,
	title = {Noble Metals on the Nanoscale: Optical and Photothermal Properties and Some Applications in Imaging, Sensing, Biology, and Medicine},
	journal = {Accounts of Chemical Research},
	volume = {41},
	number = {12},
	year = {2008},
	note = {Jain, Prashant K. Huang, Xiaohua El-Sayed, Ivan H. El-Sayed, Mostafa A.},
	month = {Dec},
	pages = {1578-1586},
	abstract = {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.},
	isbn = {0001-4842},
	doi = {10.1021/ar7002804},
	author = {Jain, Prashant K and Huang, Xiaohua and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1127,
	title = {Plasmonic photothermal therapy (PPTT) using gold nanoparticles},
	journal = {Lasers in Medical Science},
	volume = {23},
	number = {3},
	year = {2008},
	note = {Huang, Xiaohua Jain, Prashant K. El-Sayed, Ivan H. El-Sayed, Mostafa A.},
	month = {Jul},
	pages = {217-228},
	abstract = {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.},
	keywords = {display},
	isbn = {0268-8921},
	doi = {10.1007/s10103-007-0470-x},
	author = {Huang, Xiaohua and Jain, Prashant K and El Sayed, I.H. and El-Sayed, Mostafa A.}
}
@article {1139,
	title = {Au nanoparticles target cancer},
	journal = {Nano Today},
	volume = {2},
	number = {1},
	year = {2007},
	note = {Jain, Prashant K. El-Sayed, Ivan H. El-Sayed, Mostafa A.},
	month = {Feb},
	pages = {18-29},
	abstract = {Nanoparticles with unique optical properties, facile surface chemistry, and appropriate size scale are generating much enthusiasm in molecular biology and medicine. Noble metal, especially Au, nanoparticles have immense potential for cancer diagnosis and therapy on account of their surface plasmon resonance (SPR) enhanced light scattering and absorption. Conjugation of Au nanoparticles to ligands specifically targeted to biomarkers on cancer cells allows molecular-specific imaging and detection of cancer. Additionally, Au nanoparticles efficiently convert the strongly absorbed light into localized heat, which can be exploited for the selective laser photothermal therapy of cancer. We discuss recent advances in the study and use of selectively targeted Au nanospheres in cancer photodiagnostics and photothermal therapy. By changing the shape or composition of Au nanoparticles, the SPR can be tuned to the near-infrared region, allowing in vivo imaging and photothermal therapy of cancer. The use of Au nanorods and silica-Au core-shell nanoparticles for in vivo cancer detection and therapy is discussed.},
	isbn = {1748-0132},
	doi = {10.1016/s1748-0132(07)70016-6},
	author = {Jain, Prashant K and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1141,
	title = {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},
	journal = {Nano Letters},
	volume = {7},
	number = {6},
	year = {2007},
	note = {Huang, Xiaohua El-Sayed, Ivan H. Qian, Wei El-Sayed, Mostafa A.},
	month = {Jun},
	pages = {1591-1597},
	abstract = {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.},
	isbn = {1530-6984},
	doi = {10.1021/nl070472c},
	author = {Huang, Xiaohua and El Sayed, I.H. and Qian, Wei and El-Sayed, Mostafa A}
}
@article {1145,
	title = {Effect of plasmonic gold nanoparticles on benign and malignant cellular autofluorescence: A novel probe for fluorescence based detection of cancer},
	journal = {Technology in Cancer Research \& Treatment},
	volume = {6},
	number = {5},
	year = {2007},
	note = {El-Sayed, Ivan Huang, Xiaohua Macheret, Fima Humstoe, Joseph Oren Kramer, Randall El-Sayed, Mostafa},
	month = {Oct},
	pages = {403-412},
	abstract = {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.},
	isbn = {1533-0346},
	author = {El Sayed, I.H. and Huang, Xiaohua and Macheret, F. and Humstoe, J. O. and Kramer, R. and El-Sayed, Mostafa A}
}
@article {1140,
	title = {Gold nanoparticles: interesting optical properties and recent applications in cancer diagnostic and therapy},
	journal = {Nanomedicine},
	volume = {2},
	number = {5},
	year = {2007},
	note = {Huang, Xiaohua Jain, Prashant K. El-Sayed, Ivan H. El-Sayed, Mostafa A.},
	month = {Oct},
	pages = {681-693},
	abstract = {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.},
	isbn = {1743-5889},
	doi = {10.2217/17435889.2.5.681},
	author = {Huang, Xiaohua and Jain, Prashant K and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1294,
	title = {Multicolorimetric plasmonic gold nanoparticles for 8 optical detection of oral squamous carcinoma},
	journal = {Oral Oncology},
	volume = {43},
	year = {2007},
	note = {El-Sayed, I. Huang, X. El-Sayed, M.1st World Congress of the International-Academy-of-Oral-OncologyMay 17-20, 2007Amsterdam, NETHERLANDSInt Acad Oral OncolS},
	month = {05/2007},
	pages = {121-121},
	issn = {1368-8375},
	author = {El Sayed, I.H. and Huang, X. and El-Sayed, Mostafa A}
}
@article {1135,
	title = {Peptide-conjugated gold nanorods for nuclear targeting},
	journal = {Bioconjugate Chemistry},
	volume = {18},
	number = {5},
	year = {2007},
	note = {Oyelere, Adegboyega K. Chen, Po C. Huang, Xiaohua El-Sayed, Ivan H. El-Sayed, Mostafa A.},
	month = {Sep-Oct},
	pages = {1490-1497},
	abstract = {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.},
	isbn = {1043-1802},
	doi = {10.1021/bc070132i},
	author = {Oyelere, A. K. and Chen, P. C. and Huang, Xiaohua and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1142,
	title = {The potential use of the enhanced nonlinear properties of gold nanospheres in photothermal cancer therapy},
	journal = {Lasers in Surgery and Medicine},
	volume = {39},
	number = {9},
	year = {2007},
	note = {Huang, Xiaohua Qian, Wei El-Sayed, Ivan H. El-Sayed, Mostafa A.},
	month = {Oct},
	pages = {747-753},
	abstract = {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.},
	isbn = {0196-8092},
	doi = {10.1002/lsm.20577},
	author = {Huang, Xiaohua and Qian, Wei and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {815,
	title = {Review of some interesting surface plasmon resonance-enhanced properties of noble metal nanoparticles and their applications to biosystems},
	journal = {Plasmonics},
	volume = {2},
	year = {2007},
	pages = {107-118},
	publisher = {Springer},
	abstract = {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.},
	isbn = {1557-1955},
	doi = {10.1007/s11468-007-9031-1},
	url = {http://dx.doi.org/10.1007/s11468-007-9031-1},
	author = {Jain, Prashant K and Huang, Xiaohua and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1150,
	title = {Calculated absorption and scattering properties of gold nanoparticles of different size, shape, and composition: Applications in biological imaging and biomedicine},
	journal = {Journal of Physical Chemistry B},
	volume = {110},
	number = {14},
	year = {2006},
	note = {Jain, PK Lee, KS El-Sayed, IH El-Sayed, MA},
	month = {Apr},
	pages = {7238-7248},
	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 (similar to 40 nm) show an absorption cross-section 5 orders higher than conventional absorbing dyes, while the magnitude of light scattering by 80-nm gold nanospheres is 5 orders higher than the light emission from strongly fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres, i.e., from similar to 520 to 550 nm, is however too limited to be useful for in vivo applications. Gold nanoshells are found to have optical cross-sections comparable to and even higher than the nanospheres. Additionally, their optical resonances lie favorably in the near-infrared region. The resonance wavelength can be rapidly increased by either increasing the total nanoshell size or increasing the ratio of the core-to-shell radius. The total extinction of nanoshells shows a linear dependence on their total size, however, it is independent of the core/shell radius ratio. The relative scattering contribution to the extinction can be rapidly increased by increasing the nanoshell size or decreasing the ratio of the core/shell radius. Gold nanorods show optical cross-sections comparable to nanospheres and nanoshells, however, at much smaller effective size. Their optical resonance can be linearly tuned across the near-infrared region by changing either the effective size or the aspect ratio of the nanorods. The total extinction as well as the relative scattering contribution increases rapidly with the effective size, however, they are independent of the aspect ratio. To compare the effectiveness of nanoparticles of different sizes for real biomedical applications, size-normalized optical cross-sections or per micron coefficients are calculated. Gold nanorods show per micron absorption and scattering coefficients that are an order of magnitude higher than those for nanoshells and nanospheres. 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 nanorods of high aspect ratio with a larger effective radius.},
	isbn = {1520-6106},
	doi = {10.1021/jp057170o},
	author = {Jain, Prashant K and Lee, K. S. and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1153,
	title = {Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods},
	journal = {Journal of the American Chemical Society},
	volume = {128},
	number = {6},
	year = {2006},
	note = {Huang, XH El-Sayed, IH Qian, W El-Sayed, MA},
	month = {Feb},
	pages = {2115-2120},
	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 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.},
	keywords = {display},
	isbn = {0002-7863},
	doi = {10.1021/ja057254a},
	author = {Huang, Xiaohua and El Sayed, I.H. and Qian, Wei and El-Sayed, Mostafa A.}
}
@article {1152,
	title = {Determination of the minimum temperature required for selective photothermal destruction of cancer cells with the use of immunotargeted gold nanoparticles},
	journal = {Photochemistry and Photobiology},
	volume = {82},
	number = {2},
	year = {2006},
	note = {Huang, XH Jain, PK El-Sayed, IH El-Sayed, MA},
	month = {Mar-Apr},
	pages = {412-417},
	abstract = {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.},
	isbn = {0031-8655},
	doi = {10.1562/2005-12-14-ra-754},
	author = {Huang, Xiaohua and Jain, Prashant K and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1158,
	title = {Selective laser photo-thermal therapy of epithelial carcinoma using anti-EGFR antibody conjugated gold nanoparticles},
	journal = {Cancer Letters},
	volume = {239},
	number = {1},
	year = {2006},
	note = {El-Sayed, Ivan H. Huang, Xiaohua El-Sayed, Mostafa A.},
	month = {Jul},
	pages = {129-135},
	abstract = {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.},
	isbn = {0304-3835},
	doi = {10.1016/j.canlet.2005.07.035},
	author = {El Sayed, I.H. and Huang, Xiaohua and El-Sayed, Mostafa A}
}
@article {1169,
	title = {Gold nanoparticles: Catalyst for the oxidation of NADH to NAD(+)},
	journal = {Journal of Photochemistry and Photobiology B-Biology},
	volume = {81},
	number = {2},
	year = {2005},
	note = {Huang, XH El-Sayed, IH Yi, XB El-Sayed, MA},
	month = {Nov},
	pages = {76-83},
	abstract = {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.},
	isbn = {1011-1344},
	doi = {10.1016/j.jphotobiol.2005.05.010},
	author = {Huang, Xiaohua and El Sayed, I.H. and Yi, X. B. and El-Sayed, Mostafa A}
}
@article {1173,
	title = {Surface plasmon resonance scattering and absorption of anti-EGFR antibody conjugated gold nanoparticles in cancer diagnostics: Applications in oral cancer},
	journal = {Nano Letters},
	volume = {5},
	number = {5},
	year = {2005},
	note = {El-Sayed, IH Huang, XH El-Sayed, MA},
	month = {May},
	pages = {829-834},
	abstract = {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.},
	keywords = {display},
	isbn = {1530-6984},
	doi = {10.1021/nl050074e},
	author = {El Sayed, I.H. and Huang, Xiaohua and El-Sayed, Mostafa A.}
}
@article {1183,
	title = {Model system for growing and quantifying Streptococcus pneumoniae biofilms in situ and in real time},
	journal = {Applied and Environmental Microbiology},
	volume = {70},
	number = {8},
	year = {2004},
	note = {Donlan, RM Piede, JA Heyes, CD Sanii, L Murga, R Edmonds, P El-Sayed, I El-Sayed, MA},
	month = {Aug},
	pages = {4980-4988},
	abstract = {Streptococcus pneumoniae forms biofilms, but little is known about its extracellular polymeric substances (EPS) or the kinetics of biofilm formation. A system was developed to enable the simultaneous measurement of cells and the EPS of biofilm-associated S. pneumoniae in situ over time. A biofilm reactor containing germanium coupons was interfaced to an attenuated total reflectance (ATR) germanium cell of a Fourier transform infrared (FTIR) laser spectrometer. Biofilm-associated cells were recovered from the coupons and quantified by total and viable cell count methods. ATR-FTIR spectroscopy of biofilms formed on the germanium internal reflection element (IRE) of the ATR cell provided a continuous spectrum of biofilm protein and polysaccharide (a measure of the EPS). Staining of the biofilms on the IRE surface with specific fluorescent probes provided confirmatory evidence for the biofilm structure and the presence of biofilm polysaccharides. Biofilm protein and polysaccharides were detected within hours after inoculation and continued to increase for the next 141 h. The polysaccharide band increased at a substantially higher rate than did the protein band, demonstrating increasing coverage of the IRE surface with biofilm polysaccharides. The biofilm total cell counts on germanium coupons stabilized after 21 h, at approximately 10(5) cells per cm(2), while viable counts decreased as the biofilm aged. This system is unique in its ability to detect and quantify biofilm-associated cells and EPS of S. pneumoniae over time by using multiple, corroborative techniques. This approach could prove useful for the study of biofilm processes of this or other microorganisms of clinical or industrial relevance.},
	isbn = {0099-2240},
	doi = {10.1128/aem.70.8.4980-4988.2004},
	author = {Donlan, R. M. and Piede, J. A. and Heyes, C D and Sanii, L. S. and Murga, R. and Edmonds, P. and El Sayed, I.H. and El-Sayed, Mostafa A}
}
@article {1284,
	title = {Fourier-transform infrared spectroscopic comparison of cultured human fibroblast and fibrosarcoma cells},
	journal = {Proceedings of SPIE},
	volume = {2389},
	year = {1995},
	month = {1995},
	pages = {543},
	publisher = {SPIE},
	abstract = {Infrared vibration spectroscopy appears to be a more powerful technique for diagnosis than visible or UV spectroscopy. Advantages of IR spectra include: 1) vibrational motion has a smaller tissue absorption coefficient than electronic motion, 2) scattering of infrared radiation has a lower cross section than visible or UV light, (these two facts allow deeper penetration of IR radiation) and 3) vibration spectra provide a better fingerprint of chemical groups present in cells than the unresolved broad electronic spectrum of biological molecules. In the present work, Fourier-transform IR spectroscopy was used to compare cultured human fibroblast and malignant fibrosarcoma cells. Significant differences were observed by comparing the spectra of the normal cells with that of the cancer cells. the PO2 symmetric stretching mode at 1082cm-1 in the cancer cell is reduced in intensity. These observations are similar to those reported previously by Wong et al in comparing the IR spectra of pairs of normal and cancerous cells from the colon and cervix. However, the observed increase in the relative intensity of the symmetric to antisymmetric CH3 bending mode are only found in fibrosarcoma and basal cell carcinoma. The decrease in intensity of the CH2 bending mode relative to that of CH3 mode was observed only for fibrosarcoma cells. This finding with paired human fibroblast and fibrosarcoma cells suggests that fatty acid chains or side chains of protein in the cancer cells are partially degraded leading to more terminal carbon. It is also possible that changes in the environment upon carcinogenesis induces a change in the relative absorption cross sections for the CH3 and CH2 bending vibrations.
},
	doi = {10.1117/12.210030},
	url = {http://dx.doi.org/10.1117/12.210030},
	author = {Yang, Difei},
	editor = {Castro, D. and El Sayed, I.H. and El-Sayed, Mostafa A and Saxton, R. and Zhang, N.}
}
@article {1274,
	title = {A Fourier-transform infrared spectroscopic comparison of cultured human fibroblast and fibrosarcoma cells: a new method for detection of malignancies},
	journal = {Journal of clinical laser medicine \& surgery},
	volume = {13},
	year = {1995},
	pages = {55-59},
	abstract = {Infrared vibration spectroscopy appears to be a more powerful technique for tumor diagnosis than visible or UV spectroscopy. In the present work, Fourier-transform infrared (FTIR) spectroscopy was used to compare cultured normal fibroblast and fibrosarcoma cells. Significant differences were observed by comparing the spectra of the normal human cells with that of the cancer cells. The PO2 symmetric stretching mode at 1082 cm-1 is shifted to a higher frequency in the cancer cell and a broad band, whose center is located at 1064 cm-1 in the cancer cell is reduced in intensity. In addition, the decrease in intensity of the CH2 bending mode relative to that of CH3 mode is detectable only in the fibrosarcoma cell. This FTIR difference between fibroblast and fibrosarcoma cells suggests that either fatty acid chains or protein side chains of the cancer cells are partially degraded resulting in more terminal carbon (e.g., CH3). It is also possible that changes in the environment upon carcinogenesis induces a change in the relative absorption cross section for CH3 and CH2 bending vibrations. These results suggest that FTIR spectroscopy may become a promising and sensitive technique for tumor identification.},
	isbn = {1044-5471},
	author = {Yang, Difei and Castro, D. and El Sayed, I.H. and El-Sayed, Mostafa A and SAXTON, R.E. and ZHANG, N.Y.I.}
}
