Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers.
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2017-08-17
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Abstract
Metastatic spread is the mechanism in more than 90 percent of cancer deaths and current therapeutic options, such as systemic chemotherapy, are often ineffective. Here we provide a proof of principle for a novel two-pronged modality referred to as Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) having the potential to safely eradicate both primary tumors and distant metastatic foci. Using a combination of immune-checkpoint inhibition and plasmonic gold nanostar (GNS)-mediated photothermal therapy, we were able to achieve complete eradication of primary treated tumors and distant untreated tumors in some mice implanted with the MB49 bladder cancer cells. Delayed rechallenge with MB49 cancer cells injection in mice that appeared cured by SYMPHONY did not lead to new tumor formation after 60 days observation, indicating that SYMPHONY treatment induced effective long-lasting immunity against MB49 cancer cells.
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Liu, Yang, Paolo Maccarini, Gregory M Palmer, Wiguins Etienne, Yulin Zhao, Chen-Ting Lee, Xiumei Ma, Brant A Inman, et al. (2017). Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers. Scientific reports, 7(1). p. 8606. 10.1038/s41598-017-09116-1 Retrieved from https://hdl.handle.net/10161/22462.
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Scholars@Duke
Gregory M. Palmer
Greg Palmer obtained his B.S. in Biomedical Engineering from Marquette University in 2000, after which he obtained his Ph.D. in BME from the University of Wisconsin, Madison. He is currently an Associate Professor in the Department of Radiation Oncology, Cancer Biology Division at Duke University Medical Center. His primary research focus has been identifying and exploiting the changes in absorption, scattering, and fluorescence properties of tissue associated with cancer progression and therapeutic response. To this end he has implemented a model-based approach for extracting absorber and scatterer properties from diffuse reflectance and fluorescence measurements. More recently he has developed quantitative imaging methodologies for intravital microscopy to characterize tumor functional and molecular response to radiation and chemotherapy. His awards have included the Jack Fowler Award from the Radiation Research Society.
Laboratory Website:
https://radonc.duke.edu/research-education/research-labs/radiation-and-cancer-biology/palmer-lab
Tuan Vo-Dinh
Dr. Tuan Vo-Dinh is R. Eugene and Susie E. Goodson Distinguished Professor of Biomedical Engineering, Professor of Chemistry, and Director of The Fitzpatrick Institute for Photonics.
Dr. Vo-Dinh’s research activities and interests involve biophotonics, nanophotonics, plasmonics, laser-excited luminescence spectroscopy, room temperature phosphorimetry, synchronous luminescence spectroscopy, and surface-enhanced Raman spectroscopy for multi-modality bioimaging, and theranostics (diagnostics and therapy) of diseases such as cancer and infectious diseases.
We have pioneered the development of a new generation of gene biosensing probes using surface-enhanced Raman scattering (SERS) detection with “Molecular Sentinels” and Plasmonic Coupling Interference (PCI) molecular probes for multiplex and label-free detection of nucleic acid biomarkers (DNA, mRNA, microRNA) in early detection of a wide variety of diseases.
In genomic and precision medicine, nucleic acid-based molecular diagnosis is of paramount importance with many advantages such as high specificity, high sensitivity, serotyping capability, and mutation detection. Using SERS-based plasmonic nanobiosensors and nanochips, we are developing novel nucleic acid detection methods that can be integrated into lab-on-a-chip systems for point-of-care diagnosis (e.g., breast, GI cancer) and global health applications (e.g., detection of malaria and dengue).
In bioimaging, we are developing a novel multifunctional gold nanostar (GNS) probe for use in multi-modality bioimaging in pre-operative scans with PET, MRI and CT, intraoperative margin delineation with optical imaging, SERS and two-photon luminescence (TPL). The GNS can be used also for cancer treatment with plasmonics enhanced photothermal therapy (PTT), thus providing an excellent platform for seamless diagnostics and therapy (i.e., theranostics). Preclinical studies have shown its great potential for cancer diagnostics and therapeutics for future clinical translation.
For fundamental studies, various nanobiosensors are being developed for monitoring intracellular parameters (e.g., pH) and biomolecular processes (e.g., apoptosis, caspases), opening the possibility for fundamental molecular biological research as well as biomedical applications (e.g., drug discovery) at the single cell level in a systems biology approach. For point of care diagnostics, nanoprobes and nanochips with highly multiplex SERS detection and imaging use artificial intelligence and machine learning for data analysis.
Our research activities in immunotherapy involve unique plasmonics-active gold “nanostars.” These star-shaped nanobodies made of gold work like “lightning rods,” concentrating the electromagnetic energy at their tips and allowing them to capture photon energy more efficiently when irradiated by laser light. Teaming with medical collaborators, we have developed a novel cancer treatment modality, called synergistic immuno photothermal nanotherapy (SYMPHONY), which combines immune-checkpoint inhibition and gold nanostar–mediated photothermal immunotherapy that can unleash the immunotherapeutic efficacy of checkpoint inhibitors. This combination treatment can eradicate the primary tumors as well as distant “untreated” tumors, and induce immunologic memory like a “anti-cancer vaccine” effect in murine model.
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