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HOUSTON, TX, United States

Carpin L.B.,Rice University | Bickford L.R.,Rice University | Agollah G.,Nanospectra Biosciences, Inc. | Yu T.-K.,Rice University | And 4 more authors.
Breast Cancer Research and Treatment | Year: 2011

Trastuzumab is a FDA-approved drug that has shown clinical efficacy against HER2+ breast cancers and is commonly used in combination with other chemotherapeutics. However, many patients are innately resistant to trastuzumab, or will develop resistance during treatment. Alternative treatments are needed for trastuzumab-resistant patients. Here, we investigate gold nanoparticle-mediated photothermal therapies as a potential alternative treatment for chemotherapy-resistant cancers. Gold nanoshell photothermal therapy destroys the tumor cells using heat, a physical mechanism, which is able to overcome the cellular adaptations that bestow trastuzumab resistance. By adding anti-HER2 to the gold surface of the nanoshells as a targeting modality, we increase the specificity of the nanoshells for HER2+ breast cancer. Silica-gold nanoshells conjugated with anti-HER2 were incubated with both trastuzumab-sensitive and trastuzumab-resistant breast cancer cells. Nanoshell binding was confirmed using two-photon laser scanning microscopy, and the cells were then ablated using a near-infrared laser. We demonstrate the successful targeting and ablation of trastuzumab-resistant cells using anti-HER2-conjugated silica-gold nanoshells and a near-infrared laser. This study suggests potential for applying gold nanoshell-mediated therapy to trastuzumab-resistant breast cancers in vivo. © 2010 Springer Science+Business Media, LLC.


Bickford L.R.,Rice University | Agollah G.,Nanospectra Biosciences, Inc. | Drezek R.,Rice University | Yu T.-K.,Rice University | Yu T.-K.,University of Texas M. D. Anderson Cancer Center
Breast Cancer Research and Treatment | Year: 2010

Obtaining negative margins is critical for breast cancer patients undergoing conservation therapy in order to reduce the reemergence of the original cancer. Currently, breast cancer tumor margins are examined in a pathology lab either while the patient is anesthetized or after the surgical procedure has been terminated. These current methods often result in cancer cells present at the surgical resection margin due to inadequate margin assessment at the point of care. Due to such limitations evident in current diagnoses, tools for increasing the accuracy and speed of tumor margin detection directly in the operating room are still needed. We are exploring the potential of using a nano-biophotonics system to facilitate intraoperative tumor margin assessment ex vivo at the cellular level. By combining bioconjugated silica-based gold nanoshells, which scatter light in the near-infrared, with a portable FDAapproved reflectance confocal microscope, we first validate the use of gold nanoshells as effective reflectance-based imaging probes by evaluating the contrast enhancement of three different HER2-overexpressing cell lines. Additionally, we demonstrate the ability to detect HER2-overexpressing cells in human tissue sections within 5 min of incubation time. This work supports the use of targeted silica-based gold nanoshells as potential real-time molecular probes for HER2-overexpression in human tissue.


Grant
Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase II | Award Amount: 750.00K | Year: 2005

The goal of this STTR Phase II Proposal is to complete development of the nanoshell-based surface enhanced Raman scattering substrate (NERS) developed in our successful Phase I work. This Phase II work will focus on commercialization of the substrate developed in Phase I by (i) refining manufacturing methods, including substrate composition, nanoshell deposition, and detection geometry to increase NERS sensitivity and (ii) developing model assay systems for conjugation of biomolecules onto the substrate for detection of relevant chemical entities. Our Phase I work demonstrated the following key elements of feasibility: (i) a nanoshell-based substrate can be reproducibly manufactured; (ii) this nanoshell-based substrate is stable under conditions expected in routine use; and (iii) this substrate reproducibly provides significant (>10^10) SERS enhancements from individual nanoshells, allowing a new level of sensitivity in Raman testing. This Phase II work will optimize the sensitivity of the substrate by optimizing anchoring and deposition methods and detection modalities. Additionally, we will develop Raman-based assays using periplasmic binding proteins as capture molecules.


Grant
Agency: National Science Foundation | Branch: | Program: STTR | Phase: Phase II | Award Amount: 392.28K | Year: 2005

This Small Business Technology Transfer Research (STTR) Phase II project proposes to develop a new treatment for cancer based upon the thermal activation of gold-coated nanoparticles. This therapeutic technique involves (a) the manufacture of new class of bio-compatible nanoparticles, optically-tunable nanoshells, designed to absorb in near-infrared wavelengths ; (b) the intravenous administration of nanoshells, which accumulate in the tumor as a result of the leaky vasculature associated with tumors ; (c) exposure of the tumor and potential routes of metastatic spread to an external laser source at near-infrared wavelengths, which are minimally absorbed by human tissue but preferentially absorbed by nanoshells, resulting in the generation of localized areas of heat by the nanoshells sufficient to result in tumor regression. The commercial application of this project will be in the area of cancer therapy. There are approximately 216,000 diagnosed cases of breast cancer in the U.S. each year. Treatment for breast cancer generally involves surgical excision, radiation, hormonal therapy and chemotherapy. The proposed treatment, offering a safer, minimally invasive and cheaper alternative, is expected to achieve a complete response in identified solid tumors, to treat otherwise inoperable tumors and to eliminate regional metastatic disease before it is clinically diagnosed.


Grant
Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase I | Award Amount: 100.00K | Year: 2005

This Phase I STTR proposal involves the design and feasibility testing of a nanoshell-based substrate for the surface enhancement of Raman Optical Activity (ROA). ROA is an extremely sensitive measurement of the vibrational optical activity that can provide molecular stereochemical information of optically active chiral molecules. ROA measurements have existed for the past thirty years but have not been widely used because of sensitivity limitations and the difficulty of making such a sensitive measurement. Nanoshells, a dielectric core surrounded by a thin metallic shell, have previous been shown to provide an electromagnetic near-field that can be engineered for significant surface enhanced Raman scattering (SERS), providing enhancements of at least 10^8 from individual nanoshells. Additionally, nanoshells can be engineered to provide these enhancements at desired wavelengths, including the near-infrared, which allows Raman sensing for biomolecules that otherwise have significant fluorescence background in the visible spectra. This objective of this proposal is to unlock the commercial potential of ROA by using a nanoshell-based substrate to achieve a surface enhancement of ROA (SEROA) signals. This proposed research will demonstrate the feasibility of using the strong electromagnetic near-field of nanoshells to enhance the ROA of optically active chiral molecules in the near-infrared

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