Dr. Songping Huang: "Synthesis of Nanoparticle-Based MRI/CT Contrast Agents and Gallium-Based Anticancer Drugs

The current research interests of Huang Group include development of nanoparticle-based contrast agents and molecular probes for in vivo imaging using MRI, CT and PET modalities and synthesis of novel biocompatible inorganic nanomaterials as delivery vehicles for radioactive and nonradioactive main-group, transition and lanthanide ions for diagnostic and therapeutic applications. We are also exploring intracellular copper trafficking and regulation as an effective strategy for anti-angiogenesis in metastatic cancer treatment as well as use of nanoparticle-based gallium compounds as anti-neoplastic drugs for cancer treatment. 

Magnetic resonance imaging (MRI) has emerged as a prominent diagnostic modality in modern medicine.  To improve the quality of image, a contrast agent (CA), is often intravenously administered.  Two types of MRI contrast agents are currently used in clinical diagnosis: T1-weighted and T2-weighted agents.  Most clinical T1 agents consist of the Gd3+ ion chelated by a polyaminopolycarboxylate ligand, while all the T2 agents are prepared from superparamagnetic metal oxide nanoparticles (SPIOs).  The commercial Gd3+-chelates have low sensitivity (relaxivity), and thus requiring a high tissue concentration to be effective for MR imaging.  In addition, such small-molecule agents lack the ability to penetrate cells, making them unsuitable for cellular imaging and drug delivery applications.  Conversely, the image contrast produced by a T2 agent is often interfered by signals caused by bleeding, calcification, metal deposits, or other background artifacts, making the interpretation of MR radiograms difficult.  We have developed a new generation of T1 contrast agents based on Prussian blue (PB) and its transition and lanthanide analogs with high relaxivity, long blood circulation times, and the ability to penetrate cells for clinical imaging and biomedical research.  One of our nanoparticulate Mn(II) agents is currently under pre-clinical evaluation as a potential oral MRI contrast agent. As the gold standard in diagnostic medicine, X-ray computed tomography (CT) often requires the use of a contrast agent as well.  Unlike MRI contrast agents, effective CT contrast agents need to contain elements of high atomic numbers as they have the ability to increase the attenuation of X-rays.  Currently, the clinical CT agents are exclusively iodinated organic compounds.  However, the use of nanoparticle-based CT contrast agents is expected to have several advantages in terms of imaging characteristics.  The heaviest stable, non-radioactive and nontoxic element with a strong X-ray attenuation power in the periodic table is bismuth (Z=83).  We are systematically investigating the design, synthesis and X-ray attenuation properties of bismuth compounds as potential nanoparticulate CT contrast agents.

Angiogenesis, also known as neovascularization, is the process of new blood vessel formation. It plays an important role in development, reproduction and wound repair. In healthy adults, both formation and growth of new blood vessels is tightly regulated and orchestrated by a variety of angiogenic factors and inhibitors in balance. On the other hand, angiogenesis is a rate-limiting event in tumorigenesis. Accordingly, excessive and abnormal blood vessel formation and growth has been established as the hallmark of cancer. This concept has inspired researchers to search for angiogenic inhibitors and to develop antiangiogenic strategies for cancer treatment in the past three decades.  It is well known that copper plays an important role in angiogenesis. Copper is found to be a common co-factor to several key angiogenic promoters or proteins involved in angiogenesis. We have developed a series of new compounds that can selectively remove cupper from cancer cells, thus disrupting the in vitro tube formation induced by several angiogenesis promoters that use copper as a co-factor, indicating that such compounds may be used as nonconventional anticancer drugs to treat metastatic cancer.

Selected Publications
  1. M. S. Kandanapitiye, C. Gunathilake, M. Jaroniec, S. D. Huang “Biocompatible D-Penicillamine Conjugated Au Nanoparticles: Targeting Intracellular Free Copper Ions for Detoxification” J. Mater. Chem. B 2015, 3, 5553-5559.
  2. M. S. Kandanapitiye, F. J. Wang, B. Valley, C. Gunathilake, M. Jaroniec, S. D. Huang “Selective Ion Exchange Governed by the Irving−Williams Series in K2Zn3[Fe(CN)6]2 Nanoparticles: Toward a Designer Prodrug for Wilson’s Disease” Inorg. Chem. 2015, 54, 1212-1214.
  3. V. S. Perera, N. P. Wickramaratne, M. Jaroniec, S. D. Huang “A Highly Efficient and Extremely Selective Intracellular Copper Detoxifying Agent Based on Nanoparticles of ZnMoS4J. Mater. Chem. B 2014, 2, 257-261.
  4. V. S. Perera, H. Liu, Z.-Q. Wang, S. D. Huang “Cell-Permeable Au@ZnMoS4 Core-Shell Nanoparticles: Toward a Novel Cellular Copper Detoxifying Drug for Wilson's Disease” Chem. Mater., 2013, 25, 4703-4709.