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Ultrasound-Sensitive Microbubble Approaches for Overcoming Tumor Hypoxia in Head and Neck SCC
Start Date: 2/4/2022Start Time: 12:00 PM
End Date: 2/22/2022End Time: 2:00 AM

Event Description
BIOMED PhD Research Proposal

Ultrasound-Sensitive Microbubble Approaches for Overcoming Tumor Hypoxia in Head and Neck Squamous Cell Carcinoma (SCC)
Quezia Lacerda, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

John R. Eisenbrey, PhD
Associate Professor
Department of Radiology
Thomas Jefferson University

Margaret A. Wheatley, PhD
John M. Reid Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. The most common malignancies of head and neck cancer arise in the mucosal epithelium in the oral cavity, pharynx and larynx. HNSCC of the oral cavity is generally treated with surgical resection, followed by radiation or chemotherapy. Unfortunately, a significant percentage of HNSCC are hypoxic (oxygen-deficient), reducing the efficacy of radiation therapy leading to poor clinical outcomes. Several methods of overcoming tumor hypoxia prior to radiation therapy have been explored but were proven ineffective. Such approaches were breathing hyperbaric oxygen, allosteric hemoglobin modifiers, hypoxia activated prodrugs and fluorocarbons (FCs). For this reason, systemic agents have been investigated for targeting the tumor’s metabolic respiration thus decreasing both growth and O2 consumption. Lonidamine (LND) has been widely explored due to its ability to target metabolic glycolysis and mitochondrial respiration in tumors. However, clinical translation has stalled due to poor bioavailability after oral administration.

Ultrasound-sensitive microbubbles containing oxygen have been proposed as a mechanism of locally overcoming tumor hypoxia prior to radiotherapy. An important property of microbubbles is ultrasound-triggered cavitation, which can take the form of either stable or inertial cavitation which bursts the bubbles. Our group demonstrated the feasibility of this approach in vivo with breast tumor xenografts using surfactant-shelled microbubbles (SE61O2) to locally release O2 while continuously monitoring tumor partial oxygen pressure (pO2). Intratumoral oxygen pressure was elevated by 19.7 ±9.1, which improved the efficacy of radiation therapy dramatically (3-4X improvement). Duration of oxygenation by this platform is limited (2-3 minutes) making clinical translation difficult. The scientific premise of this work is that we can overcome the translational limitations of our group’s current O2 microbubble platform by including the therapeutic agent LND to target cellular respiration in tumors. We will also validate the potential of this combined approach for HNSCC treatment in a clinically relevant setting. Specifically, we will encapsulate LND within the hydrophobic portion of the surfactant shell in the hopes that treatment could be further augmented with co-delivery of LND along with oxygen. We hypothesize that localized, ultrasound-directed delivery of these microbubbles will demonstrate similar levels of increased oxygenation to our previous designs, and that the addition of LND will prolong oxygenation time, enabling sufficient time for CT guided radiotherapy.

The proposed project aims to develop a minimally invasive and clinically translatable method for overcoming tumor hypoxia prior to radiotherapy. We expect this platform will improve tumoral response to radiotherapy and potentially reduce the frequency of recurrence and metastasis of HNSCC and ultimately improving patient outcomes.
Contact Information:
Name: Natalia Broz
Email: njb33@drexel.edu
Quezia Lacerda
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