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

By Geo ﬀ rey von Maltzahn, Ji-Ho Park, A. Agrawal, N. K. Bandaru, Sarit K. Das, Michael J. Sailor, Sangeeta N. Bhatia. Cancer Research, 2009

1,010 citations recorded by the source corpus.

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 (t1/2, ~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.

Subfields: Biomedical Engineering, Electronic, Optical and Magnetic Materials, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3fe2fdb405c617377bfc9013fdcf7ba695e8867b

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Citations in the corpus

Toxicity and cellular uptake of gold nanoparticles: what we have learned so far? (2010, neutral): “In this study, the total dose of nanorods required for complete photothermal destruction of the tumor was 20 mg/kg (in gold atoms) and did not induce any toxicity in tumor-free mice (von Maltzahn et al. 2009).”
Assessment of the Evolution of Cancer Treatment Therapies (2011, background): “[92] demonstrated that (PEG)–protected gold nanorods exhibit superior spectral bandwidth, higher photothermal heat generation per gram of gold and longer circulation half-life when compared to gold nanoshells, as well as an approximately two-fold higher X-ray absorption than a clinical iodine contra”
Nanoparticles that Communicate In Vivo to Amplify Tumour Targeting (2011, methodology): “MDA-MB-435 human cancer cells were cultured as recommended by ATCC and injected into nu/nu mice to establish xenograft tumours as described previously (3, 11, 23).”
PEGylation as a strategy for improving nanoparticle-based drug and gene delivery (2015, neutral): ““stealth” properties provided by surface PEG coatings [9, 36].”
Gold nanoparticles: Optical properties and implementations in cancer diagnosis and photothermal therapy (2010, background): “Recent studies have shown that PEGylated gold nanorods has a blood half-life time over 17 h in mice [138].”