Fitzpatrick Institute for Photonics

Durham, NC, United States

Fitzpatrick Institute for Photonics

Durham, NC, United States
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News Article | August 17, 2017
Site: phys.org

The potent combination also attacked satellite tumors and distant cancerous cells, completely curing two mice and effectively vaccinating one against the disease. The results appeared online in Scientific Reports on August 17. "The ideal cancer treatment is non-invasive, safe and uses multiple approaches," said Tuan Vo-Dinh, the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, professor of chemistry, and director of the Fitzpatrick Institute for Photonics at Duke University. "We also aim at activating the patient's own immune system to eradicate residual metastatic tumors. If we can create a long-term anticancer immunity, then we'd truly have a cure." The new approach relies on a "photothermal immunotherapy" technology developed by an interdisciplinary group of Duke researchers that uses lasers and gold nanostars to heat up and destroy tumors in combination with an immunotherapeutic drug. This photothermal therapy hinges on the widely demonstrated fact that nanoparticles accumulate preferentially within a tumor due to its leaky vasculature. While several researchers around the world are pursuing such techniques using nanoparticles, Vo-Dinh has pioneered the development of a unique type of nanoparticles called gold nanostars, which have the advantage of geometry. Because gold nanostars have multiple sharp spikes, they are able to capture the laser's energy more efficiently. This allows them work with less exposure, making them more effective deeper within a tissue. "The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips," said Vo-Dinh. "We've experimented with these gold nanostars to treat tumors before, but we wanted to know if we could also treat tumors we didn't even know were there or tumors that have spread throughout the body." To attack distant cancerous cells outside of the treatment site, Vo-Dinh teamed up with colleagues Brant Inman and Greg Palmer in the Departments of Surgery and Radiation Oncology at Duke University Medical Center, and Paolo Maccarini of Duke Biomedical Engineering. They combined this gold nanostar therapy with a cancer immunotherapy recently cleared by the FDA and in clinical use. Normally, the body's immune system protects against the growth of cancerous cells. Many tumors, however, overproduce a molecule called PD-L1, which effectively disables T cells, the immune system's main soldiers. Several pharmaceuticals are being developed to attempt to block the action of PD-L1, allowing the immune system to destroy the cancerous cells. Inman has been active in the early development and current clinical use of these drugs—which were used in this study—to treat bladder cancer. In the experiment, the Duke researchers injected bladder cancer cells into both hind legs of a group of mice. After waiting for the tumors to grow, the researchers began trying different types of treatments—but only on one of the legs. Those that received no treatments all quickly succumbed to the cancer, as did those receiving only the gold nanostar phototherapy, because the treatment did nothing to affect the tumor in the untreated leg. While a few mice responded well to the immunotherapy alone, with the drug stalling both tumors, none survived more than 49 days. The group treated with both the immunotherapy and the gold nanostar phototherapy fared much better, with two of the five mice surviving more than 55 days. "When a tumor dies, it releases particles that trigger the immune system to attack the remnants," said Vo-Dinh. "By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding." The combined treatment worked so well that, in a bit of a surprise, one mouse is still alive nearly a year out with zero recurrence of the cancer. Even a month later, when the researchers injected more cancerous cells, the mouse's immune system attacked and destroyed them without a problem indicating a vaccine effect in the cured mouse. "This is our goal—our dream," said Vo-Dinh. While researchers conducted this proof-of-concept experiment with a small number of mice, the results are encouraging. The Duke researchers now plan to follow up with larger cohorts and to work with other clinical researchers to test the treatment on mouse models of brain, breast and lung cancer. Explore further: Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer More information: Yang Liu et al, Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers, Scientific Reports (2017). DOI: 10.1038/s41598-017-09116-1


News Article | August 17, 2017
Site: www.eurekalert.org

DURHAM, N.C. -- By combining an FDA-approved cancer immunotherapy with an emerging tumor-roasting nanotechnology, Duke University researchers improved the efficacy of both therapies in a proof-of-concept study using mice. The potent combination also attacked satellite tumors and distant cancerous cells, completely curing two mice and effectively vaccinating one against the disease. The results appeared online in Scientific Reports on August 17. "The ideal cancer treatment is non-invasive, safe and uses multiple approaches," said Tuan Vo-Dinh, the R. Eugene and Susie E. Goodson Professor of Biomedical Engineering, professor of chemistry, and director of the Fitzpatrick Institute for Photonics at Duke University. "We also aim at activating the patient's own immune system to eradicate residual metastatic tumors. If we can create a long-term anticancer immunity, then we'd truly have a cure." The new approach relies on a "photothermal immunotherapy" technology developed by an interdisciplinary group of Duke researchers that uses lasers and gold nanostars to heat up and destroy tumors in combination with an immunotherapeutic drug. This photothermal therapy hinges on the widely demonstrated fact that nanoparticles accumulate preferentially within a tumor due to its leaky vasculature. While several researchers around the world are pursuing such techniques using nanoparticles, Vo-Dinh has pioneered the development of a unique type of nanoparticles called gold nanostars, which have the advantage of geometry. Because gold nanostars have multiple sharp spikes, they are able to capture the laser's energy more efficiently. This allows them work with less exposure, making them more effective deeper within a tissue. "The nanostar spikes work like lightning rods, concentrating the electromagnetic energy at their tips," said Vo-Dinh. "We've experimented with these gold nanostars to treat tumors before, but we wanted to know if we could also treat tumors we didn't even know were there or tumors that have spread throughout the body." To attack distant cancerous cells outside of the treatment site, Vo-Dinh teamed up with colleagues Brant Inman and Greg Palmer in the Departments of Surgery and Radiation Oncology at Duke University Medical Center, and Paolo Maccarini of Duke Biomedical Engineering. They combined this gold nanostar therapy with a cancer immunotherapy recently cleared by the FDA and in clinical use. Normally, the body's immune system protects against the growth of cancerous cells. Many tumors, however, overproduce a molecule called PD-L1, which effectively disables T cells, the immune system's main soldiers. Several pharmaceuticals are being developed to attempt to block the action of PD-L1, allowing the immune system to destroy the cancerous cells. Inman has been active in the early development and current clinical use of these drugs -- which were used in this study -- to treat bladder cancer. In the experiment, the Duke researchers injected bladder cancer cells into both hind legs of a group of mice. After waiting for the tumors to grow, the researchers began trying different types of treatments -- but only on one of the legs. Those that received no treatments all quickly succumbed to the cancer, as did those receiving only the gold nanostar phototherapy, because the treatment did nothing to affect the tumor in the untreated leg. While a few mice responded well to the immunotherapy alone, with the drug stalling both tumors, none survived more than 49 days. The group treated with both the immunotherapy and the gold nanostar phototherapy fared much better, with two of the five mice surviving more than 55 days. "When a tumor dies, it releases particles that trigger the immune system to attack the remnants," said Vo-Dinh. "By destroying the primary tumor, we activated the immune system against the remaining cancerous cells, and the immunotherapy prevented them from hiding." The combined treatment worked so well that, in a bit of a surprise, one mouse is still alive nearly a year out with zero recurrence of the cancer. Even a month later, when the researchers injected more cancerous cells, the mouse's immune system attacked and destroyed them without a problem indicating a vaccine effect in the cured mouse. "This is our goal -- our dream," said Vo-Dinh. While researchers conducted this proof-of-concept experiment with a small number of mice, the results are encouraging. The Duke researchers now plan to follow up with larger cohorts and to work with other clinical researchers to test the treatment on mouse models of brain, breast and lung cancer. "Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers." Yang Liu, Paolo Maccarini, Gregory M. Palmer, Wiguins Etienne, Yulin Zhao, Chen-Ting Lee, Xiumei Ma, Brant A. Inman & Tuan Vo-Dinh. Scientific Reports, 2017. DOI: 10.1038/s41598-017-09116-1


Chowdhury S.,Fitzpatrick Institute for Photonics | Eldridge W.J.,Fitzpatrick Institute for Photonics | Wax A.,Fitzpatrick Institute for Photonics | Izatt J.,Fitzpatrick Institute for Photonics
Optica | Year: 2017

To probe biological questions with significant biophysical, biochemical, and molecular components, an imaging solution compatible with both endogenous and molecular 3D imaging may be necessary. In this work, we show that structured illumination (SI) microscopy, popularly associated with 3D fluorescent super-resolution, can allow 3D refractive index (RI) reconstructions when operated in the coherent realm. We introduce a novel reinterpretation of coherent SI, which mathematically equates it to a superposition of angled illuminations. Raw acquisitions for standard SI-enhanced quantitative-phase images can be processed into electric field maps of the sample under angled illuminations. Standard diffraction tomography (DT) computation can then be used to reconstruct the sample’s 3D RI distribution at sub-diffraction resolutions. We demonstrate this concept by using SI to computationally reconstruct 3D RI distributions of human breast (MCF-7) and colorectal (HT-29) adenocarcinoma cells. Our experimental setup generates SI patterns using broadband illumination with a spatial light modulator and detects angledependent sample diffraction through a common-path, off-axis interferometer with no moving components. This technique may easily pair with SI fluorescence microscopy and important future extensions may include multimodal, sub-diffraction resolution, 3D RI, and fluorescent visualizations. © 2017 Optical Society of America.


Chowdhury S.,Fitzpatrick Institute for Photonics | Eldridge W.J.,Fitzpatrick Institute for Photonics | Wax A.,Fitzpatrick Institute for Photonics | Izatt J.A.,Fitzpatrick Institute for Photonics
Biomedical Optics Express | Year: 2017

Sub-diffraction resolution imaging has played a pivotal role in biological research by visualizing key, but previously unresolvable, sub-cellular structures. Unfortunately, applications of far-field sub-diffraction resolution are currently divided between fluorescent and coherent-diffraction regimes, and a multimodal sub-diffraction technique that bridges this gap has not yet been demonstrated. Here we report that structured illumination (SI) allows multimodal sub-diffraction imaging of both coherent quantitative-phase (QP) and fluorescence. Due to SI’s conventionally fluorescent applications, we first demonstrate the principle of SI-enabled three-dimensional (3D) QP sub-diffraction imaging with calibration microspheres. Image analysis confirmed enhanced lateral and axial resolutions over diffraction-limited QP imaging, and established striking parallels between coherent SI and conventional optical diffraction tomography. We next introduce an optical system utilizing SI to achieve 3D sub-diffraction, multimodal QP/fluorescent visualization of A549 biological cells fluorescently tagged for F-actin. Our results suggest that SI has a unique utility in studying biological phenomena with significant molecular, biophysical, and biochemical components. © 2017 Optical Society of America.


Correia-Ledo D.,University of Montréal | Gibson K.F.,University of Strathclyde | Dhawan A.,Indian Institute of Technology Delhi | Dhawan A.,Fitzpatrick Institute for Photonics | And 6 more authors.
Journal of Physical Chemistry C | Year: 2012

The increasing popularity of surface plasmon resonance (SPR) and surface enhanced Raman scattering (SERS) sensor design based on nanotriangle or nanohole arrays, and the possibility to manufacture substrates at the transition between these plasmonic substrates, makes them ideal candidates for the establishment of structure-property relationships. This work features near diffraction-limited Raman images and finite-difference time-domain (FDTD) simulations of nanotriangle and nanohole array substrates, which clearly demonstrate that the localization of the hot spot on these SERS substrates is significantly influenced by the ratio of diameter/periodicity (D/P). The experimental and simulation data reveal that the hot spots are located around nanotriangles (D/P = 1), characteristic of localized SPR. Decreasing the D/P ratio to 0.75-0.7 led to the creation of nanohole arrays, which promoted the excitation of a propagating surface plasmon (SP) delocalized over the metal network. The optimal SERS intensity was consistently achieved at this transition from nanotriangles to nanoholes, for every periodicity (650 nm to 1.5 μm) and excitation wavelength (633 and 785 nm) investigated, despite the presence or absence of a plasmonic band near the laser excitation. Further decreasing the D/P ratio led to excitation of a localized SP located around the rim of nanohole arrays for D/P of 0.5-0.6, in agreement with previous reports. In addition, this manuscript provides the first evidence that the hot spots are positioned inside the hole for D/P of 0.4, with the center being the region of highest electric field and Raman intensity. The compelling experimental evidence and FDTD simulations offer an overall understanding of the plasmonic properties of nanohole arrays as SERS and SPR sensors, which is of significant value in advancing the diversity of applications from such surfaces. © 2012 American Chemical Society.


Vo-Dinh T.,Fitzpatrick Institute for Photonics | Vo-Dinh T.,Duke University | Liu Y.,Fitzpatrick Institute for Photonics | Liu Y.,Duke University | And 14 more authors.
Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology | Year: 2015

This article provides an overview of recent developments and applications of surface-enhanced Raman scattering (SERS) nanosensors and nanoreporters in our laboratory for use in biochemical monitoring, medical diagnostics, and therapy. The design and fabrication of different types of plasmonics-active nanostructures are discussed. The SERS nanosensors can be used in various applications including pH sensing, protein detection, and gene diagnostics. For DNA detection the 'Molecular Sentinel' nanoprobe can be used as a homogenous bioassay in solution or on a chip platform. Gold nanostars provide an excellent multi-modality theranostic platform, combining Raman and SERS with two-photon luminescence (TPL) imaging as well as photodynamic therapy (PDT), and photothermal therapy (PTT). Plasmonics-enhanced and optically modulated delivery of nanostars into brain tumor in live animals was demonstrated; photothermal treatment of tumor vasculature may induce inflammasome activation, thus increasing the permeability of the blood brain-tumor barrier. The imaging method using TPL of gold nanostars provides an unprecedented spatial selectivity for enhanced targeted nanostar delivery to cortical tumor tissue. A quintuple-modality nanoreporter based on gold nanostars for SERS, TPL, magnetic resonance imaging (MRI), computed tomography (CT), and PTT has recently been developed. The possibility of combining spectral selectivity and high sensitivity of the SERS process with the inherent molecular specificity of bioreceptor-based nanoprobes provides a unique multiplex and selective diagnostic modality. Several examples of optical detection using SERS in combination with other detection and treatment modalities are discussed to illustrate the usefulness and potential of SERS nanosensors and nanoreporters for medical applications. © 2014 Wiley Periodicals, Inc.

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