The Brain Tumor Nanotechnology (BTN) Laboratory at the UPMC Hillman Cancer Center is a bench top and translational lab with a focus on the preclinical testing of nanoparticle constructs for the targeted imaging and therapy of patient-based brain tumor models both in cell culture and in animal models. Led by principal investigator Constantinos Hadjipanayis MD, PhD—executive vice-chair of the University of Pittsburgh Department of Neurological Surgery, director of the UPMC Center for Image-Guided Neurosurgery, and co-director of the UPMC Hillman Brain Tumor Center—current activities include brain tumor cell targeting, uptake, downstream signaling pathways, imaging, and therapy efficacy evaluation. The main goal of the lab is to facilitate translation of preclinical work into human clinical studies for brain tumor patients. The BTN lab is comprised of postdoctoral fellows, medical students, and a laboratory technician. Current daily activities of the BTN lab are overseen by Alexandros Bouras, MD, who is the BTN lab manager.
The lab is actively studying the use of alternating magnetic fields (AMFs) with magnetic iron-oxide nanoparticles (MIONPs) for magnetic hyperthermia therapy (MHT) of brain tumors. MHT is felt to enhance the effects of radiation therapy (RT)/chemotherapy and disrupt the blood brain barrier (BBB). As part of an established NIH R01 grant, the lab has established a multidisciplinary (neurosurgery, radiation oncology, biomedical engineering, neuroimaging, and veterinary medicine) and interinstitutional collaboration with Johns Hopkins University and Pennsylvania State University to translate MHT in combination with adjuvant therapies to GBM patients. This effort includes a clinical proof-of-concept trial in spontaneous canine glioma patients. A new collaboration with BluePearl Vet Hospital in Pittsburgh is now being established to further study MHT in canine glioma patients and further define the tumor immune microenvironment with sophisticated imaging and tissue-based studies. This vet hospital is a major referral center for neuro-oncology and offers comprehensive clinical care through an integrative approach which will further facilitate and optimize the translational potential for MHT of GBM.
The BTN lab is also involved in the study of photodynamic therapy (PDT) as a potential adjuvant therapy for malignant brain tumors. PDT is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength. 5-aminolevulinic acid (5-ALA) is a photosensitizing precursor that can be used for PDT and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. The porphyrin derivate verteporfin (VP) can penetrate the brain, pharmacologically target glioma cells, inhibit tumor invasion and is a potent chemotherapeutic agent that is also FDA approved for PDT in macular degeneration. The lab is actively studying both 5-ALA- and VP-mediated PDT in combination with RT and chemotherapy in cell culture and rodent models for the treatment of GBM. In this context, the BTN lab has established a collaboration with Huang Chiao Huang, PhD, a professor of bioengineering at the University of Maryland, to perform preclinical studies to test a proprietary formulation of VP, which may be a more potent PDT agent compared to the existing FDA approved formulation. The lab is planning to assess the feasibility and safety of intraoperative PDT utilizing VP after partial surgical resection in canine patients with spontaneous gliomas in collaboration with BluePearl Vet Hospital.
Combination therapies resulting in both radiosensitivity and chemosensitivity enhancement of malignant brain tumors are studied as well in the BTN lab. Various patient-based rodent brain tumor models are used for therapeutic efficacy and safety studies. Another focus of the lab is the study of DNA damage signaling and response to therapy. Inhibitors of the DNA damage signaling kinase ATR (ATRis) can potentiate tumor cell killing induced by both chemotherapy and radiation therapy (RT). Moreover, ATRis in combination with RT have exhibited immunomodulatory effects in mouse tumor models. In this context, the lab has established a collaboration with Christopher Bakkenist, PhD, a professor of radiation oncology at UPMC Hillman Cancer Center, to evaluate the potential therapeutic efficacy of ATRis in combination with RT and chemotherapy in the treatment of glioblastoma (GBM). Preclinical studies will be conducted in patient-derived brain tumor models both in cell culture and in rodent models to determine therapeutic efficacy and toxicity.
For more detailed information on the Brain Tumor Nanotechnology Laboratory at the UPMC Hillman Cancer Center, please visit pittbtnlab.com.