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

¹Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts; ²Materials Science and Engineering Program, Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California; ³Department of Mechanical Engineering, Indian Institute of Technology Madras, Chennai, India; and ⁴Howard Hughes Medical Institute and Electrical Engineering and Computer Science, Massachusetts Institute of Technology/Brigham and Women's Hospital, Boston, Massachusetts

	Abstract

Plasmonic nanomaterials have the opportunity to considerably improve the specificity of cancer ablation by i.v. homing to tumors and acting as antennas for accepting externally applied energy. Here, we describe an integrated approach to improved plasmonic therapy composed of multimodal nanomaterial optimization and computational irradiation protocol development. We synthesized polyethylene glycol (PEG)–protected gold nanorods (NR) that exhibit superior spectral bandwidth, photothermal heat generation per gram of gold, and circulation half-life in vivo (t_1/2, 17 hours) compared with the prototypical tunable plasmonic particles, gold nanoshells, as well as 2-fold higher X-ray absorption than a clinical iodine contrast agent. After intratumoral or i.v. administration, we fuse PEG-NR biodistribution data derived via noninvasive X-ray computed tomography or ex vivo spectrometry, respectively, with four-dimensional computational heat transport modeling to predict photothermal heating during irradiation. In computationally driven pilot therapeutic studies, we show that a single i.v. injection of PEG-NRs enabled destruction of all irradiated human xenograft tumors in mice. These studies highlight the potential of integrating computational therapy design with nanotherapeutic development for ultraselective tumor ablation. [Cancer Res 2009;69(9):OF1–9]

Key Words: therapy, nanoparticle, ablation, antenna, nanoantenna, gold, photothermal, computational