Nanoshells with Targeted Simultaneous Enhancement of Magnetic and Optical Imaging and Photothermal Therapeutic Response By Rizia Bardhan, Wenxue Chen, Carlos Perez-Torres, Marc Bartels, Ryan M. Huschka, Liang L. Zhao, Emilia Morosan, Robia G. Pautler, Amit Joshi,* and Naomi J. Halas* 1. Introduction The rapid development of noninvasive diagnostic imaging modalities such as magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI) has revolutionized biomedical research and practice. [1–3] Each imaging technique has its own merits and drawbacks in terms of sensitiv- ity, resolution, data acquisition time, and complexity. While numerous contrast agents for biological image enhancement have been developed in the past decade, they have most often been limited to the enhancement of a single modality. [4,5] Contrast agents that enhance more than one imaging method provide a very impor- tant advance, enabling the use of multiple modalities to probe the same system, yielding more information than any single imaging method alone. [6,7] For example, multimodal contrast agents that simulta- neously enhance MRI and FOI would combine the high sensitivity of FOI with the high spatial resolution of MRI. [8] In practice, such a dual- modality contrast agent could be used in a single clinical procedure, for pre- and post-operative MRI, then for intraoperative FOI, providing enhanced imaging before, during, and after the procedure. [6,9] The addition of antibody targeting, so that the nanocomplex can bind to the surface receptors of specific cell types in the case of cancer, along with a therapeutic function, such as photothermal heating to induce cell death, would provide a full theranostic spectrum of capabilities in a single, practical nanocomplex. The availability of multiple diagnostic and therapeutic modalities in a single agent will streamline the regulatory processed in the pharmaceutical drug development pipeline, and thus significantly reduce the cost and complexity involved in translating novel therapies from in vitro and in vivo settings to human applications. Here we report the design and demonstration of Au nanoshell- based, targeted, multimodality contrast agents in the near-IR (NIR) for MRI and FOI, which also possess an effective photothermal therapeutic response. Nanoshells (NS), consisting of a spherical dielectric core coated with a thin metallic shell, are ideal nanostructures for fabrication of these multifunctional probes. Their plasmon-derived optical resonance can be easily tuned to the NIR region of the spectrum, where tissue is maximally trans- parent, by modification of their core and shell dimensions. [10] This enables a broad range of diagnostic and therapeutic applications including optical imaging and photothermal cancer therapy. [11,12] The plasmonic properties of nanoshells can also provide a significant fluorescence enhancement of NIR fluorescent FULL PAPER www.MaterialsViews.com www.afm-journal.de [*] Prof. A. Joshi, Dr. W. Chen, Dr. M. Bartels Department of Radiology Baylor College of Medicine Houston, TX 77005 (USA) E-mail: amitj@bcm.tmc.edu Prof. N. J. Halas, R. Bardhan, R. M. Huschka Department of Chemistry Rice University, Houston, TX 77005 (USA) E-mail: halas@rice.edu Prof. N. J. Halas Departments of Electrical and Computer Engineering and Bioengineering Rice University, Houston, TX 77005 (USA) C. Perez-Torres, Prof. R. G. Pautler Department of Molecular Physiology and Biophysics Baylor College of Medicine Houston, TX 77005 (USA) L. L. Zhao, Prof. E. Morosan Department of Physics and Astronomy Rice University Houston, TX 77005 (USA) DOI: 10.1002/adfm.200901235 Integrating multiple functionalities into individual nanoscale complexes is of tremendous importance in biomedicine, expanding the capabilities of nanoscale structures to perform multiple parallel tasks. Here, the ability to enhance two different imaging technologies simultaneously—fluorescence optical imaging and magnetic resonance imaging—with antibody targeting and photothermal therapeutic actuation is combined all within the same nanoshell-based complex. The nanocomplexes are constructed by coating a gold nanoshell with a silica epilayer doped with Fe 3 O 4 and the fluorophore ICG, which results in a high T 2 relaxivity (390 mM 1 s 1 ) and 45T fluorescence enhancement of ICG. Bioconjugate nanocomplexes target HER2R cells and induce photothermal cell death upon near-IR illumination. Adv. Funct. Mater. 2009, 19, 3901–3909 ß 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim 3901