Computationally guided photothermal tumor therapy using long-circulating gold nanorod antennas.
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), approximately 17 hours) compared with the prototypical tunable plasmonic particles, gold nanoshells, as well as approximately 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.
Division of Health Sciences and Technology, Harvard-Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Geoffrey
G
von Maltzahn
Ji-Ho
JH
Park
Amit
A
Agrawal
Nanda Kishor
NK
Bandaru
Sarit K
SK
Das
Michael J
MJ
Sailor
Sangeeta N
SN
Bhatia
D000818:Animals; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006979:Hyperthermia, Induced / Q000295:instrumentation* / Q000379:methods; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D043942:Nanotubes / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D019265:Spectroscopy, Near-Infrared; D020349:Surface Plasmon Resonance; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays
D011092:Polyethylene Glycols; D006046:Gold