Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Major/Program

Biomedical Engineering

First Advisor's Name

Anthony J. McGoron

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Yen-Chih Huang

Third Advisor's Name

Chenzhong Li

Fourth Advisor's Name

Wei-Chiang Lin

Fifth Advisor's Name

Fenfei Leng

Keywords

Cancer, hyperthermia, image-guided therapy, IR820, nanoconjugate, theranostics

Date of Defense

1-16-2013

Abstract

Near-infrared dyes can be used as theranostic agents in cancer management based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and non-specific biodistribution. We studied the applications of IR820 in optical imaging and hyperthermia, and we prepared nanoconjugate formulations to overcome some of the aforementioned limitations. Free IR820 can be used for optical imaging, with a strong signal still present 24 hours after i.v. injection, an elimination plasma half-life in the order of hours, and primary biodistribution to liver, lung, and kidneys. After 808-mn laser exposure, IR820 can also raise in vitro temperatures to the 41-43°C range that can selectively inhibit cancer cell growth. We conjugated IR820 with PEG-diamine via ionic interactions to create nanoconjugates (IR820-PDNCs) with diameters of approximately 50-nm per SEM and a zeta potential of 2.0±0.9 mV. IR820-PDNCs enhanced cellular internalization compared to IR820 for imaging in SKOV-3, MES-SA, and Dx5 cancer cells. The nanoconjugates also significantly enhanced hyperthermia-mediated cytotoxicity in MES-SA and Dx5 compared to the free dye (p

Identifier

FI13041501

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