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Abstract:
Previously, the successful delivery of RNase A modified with a reactive oxygen species
(ROS) responsive modification (RNase A-NBC) to tumor cells, showed cancer specific
induced cytotoxicity. Here, we propose a novel combination formulation comprised of
Glucose Oxidase (GOx), a ROS-generating protein, and RNase A-NBC delivered using
lipidoid nanoparticles. The feasibility and ... read moreoptimization of this combination formulation
was first evaluated based on the toxicity of each protein independently delivered to
HeLa tumor cells. Subsequently, the lipidoid co-delivery of proteins was evaluated and
optimized. In addition, the combination formulation demonstrated a synergistic drug
effect as it induced a higher death rate of HeLa cells than the arithmetic sum of GOx or
RNase A-NBC alone. Finally, the glucose dependence of the cytotoxicity was also
demonstrated by GLUT inhibition experiments. These results suggest a strong potential
for this GOx & RNase A-NBC combination formulation to be applied in future cancer
treatment.
Thesis (M.S.)--Tufts University,
2015.
Submitted to the Dept. of Biomedical
Engineering.
Advisor: Qiaobing
Xu.
Committee: Ayse Asatekin, and Lauren
Black.
Keyword: Biomedical
engineering.read less
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