Date of Award
Master of Science in Chemistry (MSChem)
Dr. Santimukul Santra, Department of Chemistry
Dr. Irene Zegar, Department of Chemistry
Dr. Dilip Paul, Department of Chemistry
Dr. Cynthia Huffman, Department of Mathematics
Magnetic Resonance Imaging (MRI) is increasingly being used as a diagnostic tool for cancer. We propose a novel molecular probe, Gadolinium-DTPA disulfide-bonded Doxorubicin (Gd-DTPA-SS-Doxo) encapsulated in iron oxide which could provide a dual modality for detecting malignant growth while simultaneously targeting treatment options. We first synthesized Gd-DTPA-SS-Doxo followed by encapsulation within the poly (acrylic acid) (PAA) coating of iron oxide nanoparticle (IONP), producing a nanoprobe (IO-Gd-DTPA-SS-Doxo) with quenched longitudinal spin lattice magnetic relaxation (T1). After receptor-mediated internalization, Gd-DTPA-SS-Doxo is released from the nanoprobe’s polymeric coating due to the acidic microenvironment of the tumor. When the molecular probe is subjected to various enzymes present in the cancerous cells, the disulfide bond of the molecular probe is cleaved. This results in an intracellular release of Gd-DTPA complex and Doxo with subsequent T1 activation and cytotoxic effect respectively. Therefore, the proposed framework would give dual mode MR imaging of malignant growth, target ability and treatment for disease.
Dous, Bayan, "SYNTHESIS OF DOXORUBICIN-BASED PRODRUG AND ACTIVATABLE MR NANOPROBE FOR THE IMAGING AND TREATMENT OF CANCER" (2018). Electronic Thesis Collection. 270.