A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.
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2015
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Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.
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Liu, Yang, Jeffrey R Ashton, Everett J Moding, Hsiangkuo Yuan, Janna K Register, Andrew M Fales, Jaeyeon Choi, Melodi J Whitley, et al. (2015). A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy. Theranostics, 5(9). pp. 946–960. 10.7150/thno.11974 Retrieved from https://hdl.handle.net/10161/11045.
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Scholars@Duke
Melodi Javid Whitley
Melodi Javid Whitley, MD, PhD
Assistant Professor of Dermatology
Assistant Program Director for Trainee Research
Director of Transplant Dermatology
I am a physician scientist focused on the dermatologic care of solid organ transplant recipients. Clinically, I manage the the complex dermatologic side effects of immunosuppression with a focus on high-risk skin cancer. My research focuses on understanding the drivers of cutaneous malignancy in this population using translational approaches.
Ganesan Vaidyanathan
Dr. Vaidyanathan is a professor in the Department of Radiology. He is a member of the Nuclear Medicine track of the Medical Physics Graduate Program. His research involves development of radiopharmaceuticals especially for oncologic applications. Some of the projects he is involved in are given below.
I. New methods of radiohalogenating antibodies and its variants
a) Development of newer residualizing agents for the radiohalogenation of internalizing monoclonal antibodies.
b) Development of fluorine-18 labeled residualizing agents for labeling nanobodies.
c) Pre-targeting approach via bioorthogonal chemistry for in vivo labeling of antibodies and nanobodies with 18F and 211At.
d) Methods to label antibodies pre-conjugated with a prosthetic group of the tin precursor of residualizing agents.
e) Multimodal prosthetic groups for labeling antibodies and peptides with multiple radioisotopes.
II. MIBG Analogs for PET imaging
Radioiodinated MIBG is used in the diagnosis of the pathophysiology of the heart as well as neuroendocrine tumors such as neuroblastoma (NB). Design and development of newer fluorine-18 labeled MIBG analogues useful in the PET imaging of NB as well as that of myocardial diseases.
III. Noninvasive Imaging of Alkylguanine-DNA alkyltransferase (AGT)
AGT is a DNA repair protein and is primarily responsible for drug resistance in alkylator chemotherapy. An inverse correlation has been established between the tumor AGT content and the therapeutic outcome. The amount of AGT varies from tumor to tumor and within a group of patients of similar cancer. Thus, it is important to quantify tumor AGT of individual patients before administering alkylator chemotherapy. Our goal is to develop radiolabeled agents with which AGT can be quantified in a noninvasive manner by PET or SPECT imaging.
IV. PSMA targeting for prostate cancer therapy
Development of At-211 labeled urea-based inhibitor of Prostate-specific membrane antigen.
Cristian Tudorel Badea
- Our lab's research focus lies primarily in developing novel quantitative imaging systems, reconstruction algorithms and analysis methods. My major expertise is in preclinical CT.
- Currently, we are particularly interested in developing novel strategies for spectral CT imaging using nanoparticle-based contrast agents for theranostics (i.e. therapy and diagnostics).
- We are also engaged in developing new approaches for multidimensional CT image reconstruction suitable to address difficult undersampling cases in cardiac and spectral CT (dual energy and photon counting) using compressed sensing and/or deep learning.
- We are involved in co-clinical cancer trials and I have served as the Principal Investigator on the U24 Duke Preclinical Research Resources for Quantitative Imaging Biomarkers part of the NCI Co-Clinical Imaging Research Resources Program network (CIRP).
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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