Abstract of "Biological Application of Magnetic Nanoparticles in Targeted Therapeutics and Diagnostics" by Aruna Sigdel, Ph.D., Brown University, May 2014 Theranostics, the combination of diagnosis and therapy, holds great promise for successful cancer therapy. It allows simultaneous monitoring of distribution, localization/release of a chemotherapy drug, and therapeutic response. Gold (Au) and iron oxide (Fe3O4) nanoparticles (NPs) have been extensively studied for the theranostic applications due to their distinguished optical/magnetic properties, their biocompatibility, and their modifiable surface chemistry. In one study, I synthesized dumbbell-like Au-Fe3O4 NPs, which are both magnetically and optically active, and functionalized them with doxorubicin (DOX, a powerful cancer therapeutic drug) on the Au side via a pH sensitive Schiff-base bond and MUC1 antibody on Fe3O4 side for breast cancer targeting (MUC1-antigen is over-expressed in 95% of breast cancer cells). The efficacies of these theranostic NPs for targeting and therapy were evaluated both in vitro and in vivo. Our data show that the theranostic NPs target breast cancer cells and release DOX in low pH lysosomes to inhibit tumor growth. They are superior to the pure therapeutic drug. I studied iron oxide (Fe3O4) nanoparticles (NPs) which are FDA approved as contrast agents in Magnetic Resonance Imaging (MRI). I synthesized, functionalized the Fe3O4 NPs with pH low insertion peptide (pHLIP) and studied their targeting ability to the cancer cells utilizing extracellular low pH environment of tumor. I also studied an alternative approach for cancer therapy without using any conventional drugs. In this study, I synthesized FeAu alloy NPs and tested their controlled Fe-release in low pH environment. FeAu alloy NPs possesses plasmonic property that can be combined with theraperutic to monitor the therapeutic response. I noticed that the release Fe(0) can catalyze H2O2 decomposition into hydroxyl radical, one of the known reactive oxygen species (ROS). The overproduction of ROS causes rapid oxidation of biomolecules, leading to cell apoptosis. My preliminary tests showed that FeAu NPs are cytotoxic to cancer cells and can be used as a new generation of therapeutic drug.
Sigdel, Aruna,
"Biological Application of Magnetic Nanoparticles in Targeted Therapeutics and Diagnostics"
(2014).
Chemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0R49P4R
