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

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 , f17 hours) compared with the prototypical tunable plasmonic particles, gold nanoshells, as well as f2-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):3892-900]

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…However, physical destruction in combination with agents can achieve cancer cell destruction by several different modes on alternative survival pathways and increases the likelihood of cancer eradication [31,32]. The use of external stimuli such as near-infrared light, ultrasound, radiation, and magnetic fields can provide an alternative method of cancer treatment with the proper nanomaterials while simultaneously releasing payload only within target regions [33,34]. Multi-modal cancer therapy utilizing chemotherapy and multifunctional nanomaterials has been shown to significantly increase the efficacy of a cancer treatment and potentially offers a better solution for overcoming resistance to chemotherapeutic agents [35,36].…”

Intelligent drug delivery systems for the treatment of solid tumors

“…Thermo-sensitive and light-sensitive nanoparticles have been developed with perhaps the most promising strategy being photo-sensitive particles that respond to photo-dynamic treatments (41,42).…”

Applications of gold nanorods in biomedical imaging and related fields

“…So gold can induce a strong X-ray attenuation and makes it an ideal candidate for CT contrast agents [48]. von Maltzahn et al [49] used PEG-functionalized GNRs for X-ray CT imaging and found that GNRs exhibited about two fold amplified X-ray contrast and much longer circulating time (17 h) compared with a clinical iodine standard per mole.…”