Article

Nanoshell-mediated photothermal therapy improves survival in a murine glioma model.

Department of Bioengineering, Rice University, 6100 Main Street MS-142, Houston, TX 77005, USA.
Journal of Neuro-Oncology (Impact Factor: 2.79). 11/2010; 104(1):55-63. DOI: 10.1007/s11060-010-0470-8
Source: PubMed

ABSTRACT We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica-gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male IcrTac:ICR-Prkdc(SCID) mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P < 0.02) and 57% of the mice in the nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma.

Download full-text

Full-text

Available from: Susan M Blaney, Dec 17, 2013
0 Followers
 · 
130 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Theranostic applications require coupling of diagnosis and therapy, a high degree of specificity and adaptability to delivery methods compatible with clinical practice. The tunable physical and biological effects of selective targeting and activation of plasmonic nanobubbles (PNB) were studied in a heterogeneous biological microenvironment of prostate cancer and stromal cells. All cells were targeted with conjugates of gold nanoparticles (NPs) through an antibody-receptor-endocytosis-nanocluster mechanism that produced NP clusters. The simultaneous pulsed optical activation of intracellular NP clusters at several wavelengths resulted in higher optical contrast and therapeutic selectivity of PNBs compared with those of gold NPs alone. The developed mechanism was termed "rainbow plasmonic nanobubbles." The cellular effect of rainbow PNBs was tuned in situ in target cells, thus supporting a theranostic algorithm of prostate cancer cell detection and follow-up guided destruction without damage to collateral cells. The specificity and tunability of PNBs is promising for theranostic applications and we discuss a fiber optic platform that will capitalize on these features to bring theranostic tools to the clinic.
    Theranostics 01/2011; 1:3-17. · 7.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This review is focused on a novel cellular probe, the plasmonic nanobubble (PNB), which has the dynamically tunable and multiple functions of imaging, diagnosis, delivery, therapy and, ultimately, theranostics. The concept of theranostics was recently introduced in order to unite the clinically important stages of treatment, namely diagnosis, therapy and therapy guidance, into one single, rapid and highly accurate procedure. Cell level theranostics will have far-reaching implications for the treatment of cancer and other diseases at their earliest stages. PNBs were developed to support cell level theranostics as a new generation of on-demand tunable cellular probes. A PNB is a transient vapor nanobubble that is generated within nanoseconds around an overheated plasmonic nanoparticle with a short laser pulse. In the short term, we expect that PNB technology will be rapidly adaptable to clinical medicine, where the single cell resolution it provides will be critical for diagnosing incipient or residual disease and eliminating cancer cells, while leaving healthy cells intact. This review discusses mechanisms of plasmonic nanobubbles and their biomedical applications with the focus on cancer cell theranostics.
    02/2011; 3(1):802-840. DOI:10.3390/cancers3010802
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hollow gold-silver nanoshells having systematically varying sizes between 40 and 100 nm were prepared. These particles consist of a hollow spherical silver shell surrounded by a thin gold layer. By varying the volume of the gold stock solution added to suspensions of small silver-core templates, we tailored the hollow gold-silver nanoshells to possess strong tunable optical extinctions that range from the visible to the near-IR spectral regions, with extinctions routinely centered at ∼950 nm. The size and morphology of these core/shell nanoparticles were characterized by dynamic light scattering (DLS), field emission scanning electron microscopy (FE-SEM), and transmission electron microscopy (TEM). Separately, X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) were used for measuring their elemental composition; UV-vis spectroscopy was used to evaluate their optical properties. Given their relatively small size compared to other nanoparticles that absorb strongly at near IR wavelengths, these easy-to-synthesize particles should find use in applications that require ultrasmall nanoparticles with extinctions comfortably beyond visible wavelengths (e.g., medicinal therapies, diagnostic imaging, nanofluidics, and display technologies).
    ACS Applied Materials & Interfaces 08/2011; 3(9):3616-24. DOI:10.1021/am2008322 · 5.90 Impact Factor