Date: Thursday, March 12, 2020
Time: 12:00 p.m.
Title: Drug Loaded Nanobubbles for Focused Ultrasound-Induced Cancer Therapy
Presenter: Yiran Zou (MASc Candidate)
Supervisor/s: Prof. Naomi Matsuura
ABSTRACT: Cancer is the leading cause of death in Canada. Chemotherapy is a commonly employed cancer treatment where toxic anti-cancer drugs are given to patients intravenously. However, this treatment is not yet optimal and common drawbacks reside in the limited drug accumulation in tumour and systemic drug circulation induced toxicity to healthy organs, leading to debilitating side effects. Blood vessels are essential for tumour growth and therefore are treated as therapeutic targets in cancer therapy, termed as antivascular therapy. One way to achieve this is via the mechanical disruption of the vessel wall using focused ultrasound stimulated bubble cavitation. Therefore, this study aims to use drug (DTX) loaded nanobubbles (NB) for combined ultrasound triggered drug delivery and antivascular therapy to achieve complementary effects for improved treatment outcomes. Compared to conventional chemotherapy, these NBs enable shielding of the drug payload before ultrasound exposure to reduce systemic toxicity and can deliver high dosage of DTX on tumour site after ultrasound stimulated cavitation. In this presentation, we will report a method of synthesizing drug-loaded nanobubbles, followed by its characterizations both in vitro and in vivo. In short, DTX-NBs are formed via a lyophilization-reconstitution method from its precursor oil droplets. 105.94 ± 21.03 micrograms of DTX was loaded onto 11.05 ± 0.13 billion bubbles containing 0.45 ± 0.03 microliter of gas per milliliter of DTX-NB suspension. DTX-NBs with a mode diameter at around 230 nm was measured and 99.5 ± 0.7 % of its population below 1 micron, demonstrating the population is within the nano-range with little batch to batch variance. At a previous reported safe gas dosage of ~ 9 microliter/kg, DTX-NB can achieve a dosage at ~ 2.12 mg/kg, comparable to that of the FDA approved clinical dosage of Taxotere®. At 200 nM, the cytotoxicity of DTX-NBs after cavitation was equivalent to that of Taxotere® (*p