Date of Award

1-1-2011

Document Type

Campus Access Thesis

Department

Biomedical Engineering

First Advisor

Xiaoming He

Abstract

Nanotechnology has the potential to improve the outcomes of cancer treatment by facilitating drug targeting, tumor imaging, and treatment enhancements. Previously, we have synthesized and characterized Pluronic F127-chitosan nanocapsules for encapsulation and temperature controlled release of small molecules which could be useful for combining with cryotherapy to achieve improved cancer treatment. To further use these nanoparticles for targeted drug delivery, we have surface-modified them with folic acid (FA, to target folate receptor overexpression in cancer cells) and/or polyethylene glycol (PEG, for stealth to minimize opsonization in serum). The surface-modified nanocapsules are thermally responsive in size, which enables encapsulation of Doxorubicin (Dox) at room temperature (when the size of the nanocapsules is approximately 220-450 nm dependent on the surface-modification) and delivery to cancer cells at 37 oC (when the nanocapsules are shrunken to approximately 35 nm). Our data indicates that surface-modification of the nanocapsules with FA (even without PEG) significantly improves cellular uptake of the encapsulated Dox into folate receptor overexpressing human breast cancer (MCF-7) cells. Considering that the encapsulated drug can accumulate specifically in a tumor because of their size (10-100 nm) and surface properties (FA modification to target cancer cells) while free drug of small molecular weight distributes throughout the body after administration, the FA modified Pluronic F127-chitosan nanocapsules could be very useful for drug delivery to minimize the systemic toxicity of free anticancer drug and enhance the outcome of cancer treatment.

Rights

© 2011, Kyle Bradley Gilstrap

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