TECHNOLOGY
Introducing the First Ultra-Focal
Nanoshell Technology
Nanospectra’s proprietary technology platform is demonstrated to be safe and effective in initial clinical trials and viable for multiple applications including solid tumors, tissue and drug delivery.
AUROLASE THERAPY
The company’s principal focus is the development of AuroLase® Therapy for the ablation of solid tumors. Nanospectra’s AuroLase Therapy utilizes the unique ‘optical tunability’ of a new class of nanoparticles, called AuroShells®. These nanoparticles absorb near-infrared wavelengths of light that harmlessly penetrate human tissue. The particles are delivered intravenously and accumulate in the tumor. Then the tumor is illuminated with a near-infrared laser. The particles selectively absorb the photonic laser energy, converting the light into heat, which in turn, destroys the tumor and the blood vessels supplying it; sparing adjacent tissue.
AuroLase Therapy is used with an FDA-cleared laser that emits near-infrared energy with the clinical study specified parameters (power, duty cycle, treatment time) and with an FDA-cleared fiber optic probe for energy delivery percutaneously. AuroShell particles (also known as “nanoshells“) consist of a gold metal shell and a non-conducting silica core and serve as the exogenous absorber of the near-infrared laser energy delivered by the probe.
AuroLase Therapy components include:
- off-the-shelf near-infrared laser source
- off-the-shelf interstitial fiber optic probe for delivery of laser energy to a site near or inside the tumor
- investigational AuroShell particles, a near-infrared absorbing, inert material designed to absorb and convert photonic laser energy into heat
AuroShells: Tumor-Specific Targeting
NORMAL VESSEL ENDOTHELIUM
- Tight junctions in endothelial layer
- Particles unable to pass from blood supply
- Cleared from bloodstream by reticuloendothelial system (RES)
TUMOR VESSEL ENDOTHELIUM
- Gaps in epithelial layer allow particles to pass from blood stream into tumor
- Enhanced Permeability & Retention (RPR) results in tumor specific accumulation of nanoshells
AuroShells are delivered intravenously and due to their small size they are able to accumulate in the tumor through its leaky vasculature. The particles are unable to access normal vasculature and therefore do not accumulate in healthy tissue. Once the particles accumulate in the tumor, the area is illuminated with a near-infrared laser at wavelengths chosen to allow the maximum penetration of light through tissue. The AuroShells are designed to absorb this wavelength and convert the photonic laser energy into heat sufficient to ablate the tumor.
AuroLase for the Ablation
of Prostate Cancer Tissue
AuroLase Therapy for prostate disease is the first and only ultra-focal tissue ablation therapy designed to maximize treatment efficacy while minimizing side effects typically associated with surgery, radiation, and traditional focal therapies. The company is currently conducting a multi-site clinical trial for prostate disease.
Tumor Ablation using AuroLase Therapy
AuroLase® Therapy combines the unique physical and optical properties of AuroShell® particles with a near-infrared laser source to thermally destroy cancer tissue without significant damage to surrounding healthy tissue.
Nanospectra’s proprietary nanoshells circulate freely in the blood stream and collect in the tumor. With state of the art imaging technology, the clinician accurately identifies the lesion and positions the optical fiber probe via targeted MRI Ultrasound fusion technology. The diseased tissue is ablated while sparing the surrounding tissue.
Performed on an outpatient basis, the AuroLase procedure results in significantly fewer side effects enabling the patient to return to a normal lifestyle within days versus weeks. In addition, patients lose no follow-on clinical options.
AuroShell particles are investigational at this current time and only available through designated FDA sanctioned clinical study sites.
SCIENTIFIC PUBLICATIONS
The following includes selected scientific publications regarding the underlying Nanospectra Biosciences technology.
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Clinical studies have been carried out for detailed measurements of the build-up and clearance of engineered gold nanoshell in the tissues of dosed mice. These optically tunable nanoshells are under consideration for a new therapy for tumors. The proposed therapy would involve the injection of the nanoshells and their preferential accumulation in tumor sites. This will be followed by irradiation with a monochromatic near infrared laser, which will induce cellular hyperthermia, thereby eradicating the tumor. Neutron activation analysis has been used for the detection and quantitation of gold, and therefore, the nanoshells, in dosing materials, blood, bones and other tissues as well as tumors at various sacrifice times following dosing. Feasibility studies have shown instrumental neutron activation analysis to be uniquely suited for detection of the gold nanoshells over a wide dynamic range. This allows for the study of high concentrations of gold in tissues which scavenge the shells from the blood (liver, spleen, kidney) as well as for much lower concentrations in those which do not (muscle, brain). In particular, the tissues from animals sacrificed after the longest post dose delay (28 days) and the control animals required experimental optimization to ensure the lowest possible determination limits. The mass of gold in the tissue samples ranged from our determination limit (about 70 pg) to a few micrograms.
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The following study examines the feasibility of nanoshell-assisted photo-thermal therapy (NAPT). This technique takes advantage of the strong near infrared (NIR) absorption of nanoshells, a new class of gold nanoparticles with tunable optical absorptivities that can undergo passive extravasation from the abnormal tumor vasculature due to their nanoscale size. Tumors were grown in immune-competent mice by subcutaneous injection of murine colon carcinoma cells (CT26.WT). Polyethylene glycol (PEG) coated nanoshells (approximately 130 nm diameter) with peak optical absorption in the NIR were intravenously injected and allowed to circulate for 6 h. Tumors were then illuminated with a diode laser (808 nm, 4 W/cm2, 3 min). All such treated tumors abated and treated mice appeared healthy and tumor free >90 days later. Control animals and additional sham-treatment animals (laser treatment without nanoshell injection) were euthanized when tumors grew to a predetermined size, which occurred 6-19 days post-treatment. This simple, non-invasive procedure shows great promise as a technique for selective photo-thermal tumor ablation.
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Au and Ag nanoshells are investigated as substrates for surface-enhanced Raman scattering (SERS). We find that SERS enhancements on nanoshell films are dramatically different from those observed on colloidal aggregates, specifically that the Ramanenhancement follows the plasmon resonance of the individual nanoparticles. Comparative finite difference time domain calculations of fields at the surface of smooth and roughened nanoshells reveal that surface roughness contributes only slightly to the total enhancement. SERS enhancements as large as 2.5 x 10(10) on Ag nanoshell films for the nonresonant molecule p-mercaptoaniline are measured.
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Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermalablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.
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Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (DeltaT = 37.4 +/- 6.6 degrees C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (DeltaT < 10 degrees C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.