%0 Journal Article %J Bioconjugate Chemistry %D 2012 %T Antiandrogen Gold Nanoparticles Dual-Target and Overcome Treatment Resistance in Hormone-Insensitive Prostate Cancer Cells %A Dreaden, E. C. %A Gryder, B. E. %A Austin, Lauren %A Defo, B. A. T. %A Hayden, S. C. %A Pi, M. %A Quarles, L. D. %A Oyelere, A. K. %A El-Sayed, M. A. %X prostate cancer is the most commonly diagnosed cancer among men in the developed countries.(1) One in six males in the U.S.(2) and one in nine males in the U.K.(3) will develop the disease at some point during their lifetime. Despite advances in prostate cancer screening, more than a quarter of a million men die from the disease every year(1) due primarily to treatment-resistance and metastasis. Colloidal nanotechnologies can provide tremendous enhancements to existing targeting/treatment strategies for prostate cancer to which malignant cells are less sensitive. Here, we show that antiandrogen gold nanoparticles-multivalent analogues of antiandrogens currently used in clinical therapy for prostate cancer-selectively engage two distinct receptors, androgen receptor (AR), a target for the treatment of prostate cancer, as well as a novel G-protein coupled receptor, GPRC6A, that is also upregulated in prostate cancer. These nanoparticles selectively accumulated in hormone-insensitive and chemotherapy resistant prostate cancer cells, bound androgen receptor with multivalent affinity, and exhibited greatly enhanced drug potency versus monovalent antiandrogens currently in clinical use Further, antiandrogen gold nanoparticles selectively stimulated GPRC6A with multivalent affinity, demonstrating that the delivery of nanoscale antiandrogens can also be facilitated by the transmembrane receptor in order to realize increasingly selective, increasingly potent therapy for treatment-resistant prostate cancers. %B Bioconjugate Chemistry %V 23 %P 1507-1512 %8 Aug %@ 1043-1802 %G eng %M WOS:000307487300002 %R 10.1021/bc300158k %0 Journal Article %J Small %D 2012 %T Small Molecule-Gold Nanorod Conjugates Selectively Target and Induce Macrophage Cytotoxicity towards Breast Cancer Cells %A Dreaden, E. C. %A Mwakwari, S. C. %A Austin, Lauren %A Kieffer, M. J. %A Oyelere, A. K. %A El-Sayed, M. A. %B Small %V 8 %P 2819-2822 %8 Sep %@ 1613-6810 %G eng %M WOS:000308874900006 %R 10.1002/smll.201200333 %0 Journal Article %J Journal of Biomedical Optics %D 2010 %T Comparative study of photothermolysis of cancer cells with nuclear-targeted or cytoplasm-targeted gold nanospheres: continuous wave or pulsed lasers %A Huang, Xiaohua %A Kang, Bin %A Qian, Wei %A Mackey, M. A. %A Chen, P. C. %A Oyelere, A. K. %A El Sayed, I.H. %A El-Sayed, Mostafa A %X 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] %B Journal of Biomedical Optics %V 15 %8 Sep-Oct %@ 1083-3668 %G eng %M WOS:000284837400056 %] 058002 %R 10.1117/1.3486538 %0 Journal Article %J Bioconjugate Chemistry %D 2009 %T Tamoxifen-Poly(ethylene glycol)-Thiol Gold Nanoparticle Conjugates: Enhanced Potency and Selective Delivery for Breast Cancer Treatment %A Dreaden, Erik %A Mwakwari, S. C. %A Sodji, Q. H. %A Oyelere, A. K. %A El-Sayed, Mostafa A %X The breast cancer treatment drug tamoxifen has been widely administered for more than three decades. This small molecule competes with 17 beta-estradiol for binding to estrogen receptor, a hormone receptor upregulated in a majority of breast cancers, Subsequently initiating programmed cell death. We have synthesized a thiol-PEoylated tamoxifen derivative that can be used to selectively target and deliver plasmonic gold nanoparticles to estrogen receptor positive breast cancer cells with tip to 2.7-fold enhanced drug potency in vitro. Optical microscopy/spectroscopy, tirne-dependent dose-response data, and estrogen competition studies indicate that augmented activity is due to increased rates of intracellular tamoxifen transport by nanoparticle endocytosis, rather than by passive diffusion of the free drug. Both ligand- and receptor-dependent intracellular delivery of gold nanoparticles suggest that plasma membrane localized estrogen receptor alpha may facilitate selective uptake and retention of this and other therapeutic nanoparticle conjugates. Combined targeting selectivity and enhanced potency provides opportunities for both multimodal endocrine treatment strategies and adjunctive laser photothermal therapy. %B Bioconjugate Chemistry %V 20 %P 2247-2253 %8 Dec %@ 1043-1802 %G eng %M WOS:000272690100006 %R 10.1021/bc9002212 %0 Journal Article %J Bioconjugate Chemistry %D 2007 %T Peptide-conjugated gold nanorods for nuclear targeting %A Oyelere, A. K. %A Chen, P. C. %A Huang, Xiaohua %A El Sayed, I.H. %A El-Sayed, Mostafa A %X 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. %B Bioconjugate Chemistry %V 18 %P 1490-1497 %8 Sep-Oct %@ 1043-1802 %G eng %M WOS:000249656100018 %R 10.1021/bc070132i