A Plasmonic Gold Nanostar Theranostic Probe for In Vivo Tumor Imaging and Photothermal Therapy.

Abstract

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.7150/thno.11974

Publication Info

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

Ashton

Jeffrey Ashton

Clinical Associate in the Department of Radiology
Whitley

Melodi Javid Whitley

Assistant Professor of Dermatology

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.

Vaidyanathan

Ganesan Vaidyanathan

Professor Emeritus in Radiology

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.

Zalutsky

Michael Rod Zalutsky

Jonathan Spicehandler, M.D. Distinguished Professor of Neuro Oncology, in the School of Medicine

The overall objective of our laboratory is the development of novel radioactive compounds for improving the diagnosis and treatment of cancer. This work primarily involves radiohalo-genation of biomolecules via site-specific approaches, generally via demetallation reactions. Radionuclides utilized for imaging include I-123, I-124 and F-18, the later two being of particular interest because they can be used for the quantification of biochemical and physiological processes in the living human through positron emission tomography. For therapy, astatine-211 decays by the emission of alpha-particles, a type of radiation considerably more cytotoxic that the beta-particles used in conventional endoradiotherapy. The range of At-211 alpha particles is only a few cell diameters, offering the possibility of extremely focal irradiation of malignant cells while leaving neighboring cells intact. Highlights of recent work include: a)
development of reagents for protein and peptide radioiodination that decrease deiodination in vivo by up to 100-fold, b) demonstration that At-211 labeled monoclonal antibodies are effective in the treatment of a rat model of neoplastic meningitis, c) synthesis of a thymidine analogue labeled with At-211 and the demonstration that this molecule is taken up in cellular DNA with highly cytotoxicity even at levels of only one atom bound per cell and d) development of
radiohalobenzylguanidines which are specifically cytotoxic for human neuroblastoma cells.

Badea

Cristian Tudorel Badea

Professor in Radiology

  • 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.



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