Medicine and Health Sciences Commons^™

Development Of Bioactive Polymers For Anticancer Sirna Therapy, Siyuan Tang

Theses & Dissertations

Pancreatic ductal adenocarcinoma is a deadly disease with limited treatment options due to late diagnosis and resistance to conventional chemotherapy. Moreover, with the decreased survival rate in the past several years, pancreatic cancer may become the second leading cause of cancer-related death by surpassing breast cancer in 2030. CXCR4/CXCL12 pathway is crucial in tumor-supporting microenvironment, tumor progression, angiogenesis, metastasis and chemotherapy resistance. Small interfering RNA (siRNA) is one of the interfering RNA (RNAi), which targets mRNA specifically then knockdowns the overexpressed oncogene. Thus, siRNA has been widely used as a therapeutic strategy for various diseases including PDAC. In the research …

Development Of Polymeric Carriers For The Treatment Of Acute Kidney Injury, Yi Chen

Theses & Dissertations

Acute kidney injury (AKI) is a major kidney disease associated with high mortality and morbidity. Long-term AKI may lead to chronic kidney disease and end-stage renal disease. Several clinical trials failed due to lack of efficacy and undesired side effects. Studies showed that macromolecular delivery systems would be a promising method to target kidney, however, little is known about how physicochemical properties affects the polymers deposition in ischemia-reperfusion (I/R) AKI.

Gene therapy has been well studied as a promising therapeutic agent for several diseases, including cancer and AKI. Although small interfering RNA (siRNA) has been commonly used to treat AKI …

Delivery Of Microrna With Cxcr4-Targeted Nanoparticles In Metastatic Cancer Treatment, Ying Xie

Theses & Dissertations

Metastasis is the main contributor to cancer-associated deaths. Inhibition of CXCR4 emerged as one promising approach in metastatic cancer therapy. MiRNAs represent a new class of therapeutics for cancer treatment through RNA interference-mediated gene silencing. Polymeric CXCR4 antagonist (PCX) is a dual-functional polycation to inhibit CXCR4 and deliver nucleic acids. This dissertation hypothesized that blockade of CXCR4 by PCX combined with delivery of miRNA cooperatively enhances metastatic cancer therapy.

In chapter 1, an overview of CXCR4 inhibition, miRNA delivery and CXCR4 targeted nanomedicine in cancer therapy is given.

Chapter 2 reports that PCX can effectively deliver miR-200c mimic and that …

Development Of Cxcr4 Inhibitors For Topical Treatment Of Psoriasis, Suthida Boonsith

Theses & Dissertations

Psoriasis is a chronic inflammatory skin disease that is often associated with systemic comorbidities and impaired skin barrier function. There are several treatment options including topical treatment with immunosuppressants, phototherapy, and systemic therapies using small molecules and biological agents. However, none of them can be regarded as a perfect solution due to their toxicity during chronic use. Recently, the CXCR4/SDF-1 axis was found to play an important role in the pathogenesis of psoriasis. AMD3100, a small molecule CXCR4 antagonist can selectively bind to CXCR4 and inhibit skin inflammation, reduce angiogenesis and infiltration of inflammatory cells. Unfortunately, AMD3100 can only be …

Development Of Cxcr4-Inhibiting Nanoparticles For The Treatment Of Metastatic Cancer, Yan Wang

Theses & Dissertations

Metastasis is the main cause of cancer mortality and morbidity, leading to several million deaths every year. Less than 20% of pancreatic cancer (PC) patients are candidates for surgery due to spread beyond the pancreas. Desmoplasia presents substantial barriers to perfusion, diffusion, and convection of antitumor therapeutics into the PC tissues. We focus on developing novel therapies that regulates tumor microenvironment, chemosensitizing tumor to therapeutics and preventing metastasis.

Gene therapy is emerging as a promising new therapeutic agents for cancer treatment. A targeted, systemic, effective and safe gene delivery system should be developed. CXCR4/SDF-1 axis plays a crucial role in …