Site-specific delivery of drugs while minimizing unwanted distribution has been one of the pursued goals in cancer therapy. In this endeavor, we have developed polymer-based drug delivery carriers, whose distribution in vivo can also be quantitatively imaged by MRI, enabling whole body, real-time mapping of drug distribution, and measurements of pharmacokinetic, pharmacodynamic, and toxicity profiles. Two innovative aspects in this proposal are 1) polymeric drug carriers with exceptional stability, large retention capacity of drugs, and versatility in assembly with diverse cancer drugs and targeting ligands and 2) novel MRI techniques for quantitative measurement of paramagnetic contrast agents in the body. These aspects fulfill the requirement for drug delivery carriers to be 'theranostic'. Motivated by our recent findings that a molecule called the intercellular adhesion molecule (ICAM)-1 is highly expressed in correlation with the malignancy of thyroid cancer, we propose to develop the theranostic drug carriers loaded with Paclitaxel as a new treatment modality of thyroid cancer.
Two specific aims that will be achieved in this proposal are: 1) Develop comprehensive protocols for production and validation of theranostic nanoparticles, and for in vitro evaluation of drug efficacy and imaging techniques;2) Determine spatiotemporal distribution of drug carriers, and therapeutic efficacy and toxicity profiles to quantitatively assss tumor-drug interactions. Overall, theranostic capability of our drug carriers will be demonstrated in ectopic and orthotopic xenografts of human thyroid carcinomas in mice, a study designed to validate developed drug carriers for future use to treat aggressive, metastatic, and radioactive iodine refractory thyroid cancer.
The treatment of most cancers is directed towards surgical resection, radiation, chemotherapy, or a multimodal therapy approach. Therapeutic techniques continue to lack selective delivery of targeted therapeutic agents, and are inadequate in mapping drug distribution in the body. We propose targeted therapy and quantitative imaging of drug distribution for novel treatment of aggressive thyroid cancers.
|Kommidi, Harikrishna; Guo, Hua; Nurili, Fuad et al. (2018) 18F-Positron Emitting/Trimethine Cyanine-Fluorescent Contrast for Image-Guided Prostate Cancer Management. J Med Chem 61:4256-4262|
|Dong, Jianwu; Chen, Feng; Zhou, Dong et al. (2017) Phase unwrapping with graph cuts optimization and dual decomposition acceleration for 3D high-resolution MRI data. Magn Reson Med 77:1353-1358|
|Park, Spencer; Shevlin, Enda; Vedvyas, Yogindra et al. (2017) Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity. Sci Rep 7:14366|
|Min, Irene M; Shevlin, Enda; Vedvyas, Yogindra et al. (2017) CAR T Therapy Targeting ICAM-1 Eliminates Advanced Human Thyroid Tumors. Clin Cancer Res 23:7569-7583|
|Vedvyas, Yogindra; Shevlin, Enda; Zaman, Marjan et al. (2016) Longitudinal PET imaging demonstrates biphasic CAR T cell responses in survivors. JCI Insight 1:e90064|
|Leelawattanachai, Jeerapond; Kwon, Keon-Woo; Michael, Praveesuda et al. (2015) Side-by-Side Comparison of Commonly Used Biomolecules That Differ in Size and Affinity on Tumor Uptake and Internalization. PLoS One 10:e0124440|
|Dong, Jianwu; Liu, Tian; Chen, Feng et al. (2015) Simultaneous phase unwrapping and removal of chemical shift (SPURS) using graph cuts: application in quantitative susceptibility mapping. IEEE Trans Med Imaging 34:531-40|
|Wang, Yi; Liu, Tian (2015) Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker. Magn Reson Med 73:82-101|