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Subject: nanotechnology

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    A Nano-Sized Approach to Exploiting the Pancreatic Tumor Microenvironment
    (North Dakota State University, 2020) Confeld, Matthew Ian
    Making up just over 3% of all new cancer cases in the United States, pancreatic cancer is not inherently a common malignant disease. Yet, it continuously is shown to be one of the most lethal and common causes of cancer death. Early detection is critical among all cancer types. However, oncologists and researchers have struggled to find effective strategies or tests to detect cancer of the pancreas early on in development. Thus, the cancer is often found late stage and requires significant chemotherapy intervention. These multi-drug treatment cocktails have shown benefit, but only in added months and not years to a patient’s life. Significant adverse effects often limit the full effective doses of treatment. In order to limit these adverse effects, as well as increase the effectiveness of treatment, we have designed, optimized, and tested unique drug carriers known as polymersomes. Using characteristics of the localized environment surrounding pancreatic tumors and the cells found therein, we created targeted therapies that are responsive and relatively selective toward cancerous cells. Herein, are found two distinct polymersomes. The first, is a low oxygen reactive drug carrier with an additional small peptide molecule that is able to penetrate dense tumor tissue and has shown decreased tumor growth of as much as 260% as compared to control samples in an animal model of pancreatic cancer. The chemical make-up of this polymersome allows for extended circulation time and a high accumulation at the tumor site. A second design, uses an intracellular enzyme to destabilize the polymersomes’ structure, which in turn, releases a selected chemotherapy drug near its intended site of action. This strategy, has shown a 10 fold increase in potency of the chemotherapy drug, as compared to when the drug is given alone and showed decreased toxicity to non-cancerous cells. It is certain that thoughtful drug delivery strategies and not just drug molecule design will be instrumental in the paradigm shift of pancreatic cancer from likely death to survival.
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    Development of Nano-Architecture Systems for High-Efficiency Tumor-Targeted Drug Delivery
    (North Dakota State University, 2021) Mamnoon, Babak
    Breast cancer is the most common malignancy and the second leading cause of death among women in the United States. The commonly used breast cancer treatment strategies include surgery, chemotherapy, radiation, and hormonal therapy. Since chemotherapeutic agents do not adequately differentiate between normal and cancerous cells, systemic toxicity and adverse effects associated with these anticancer drugs limit their therapeutic efficacy. In addition, uncontrolled cell proliferation and insufficient blood supply produce low oxygen partial pressure or hypoxia in almost all solid tumors. Hypoxia increases cancer cell survival through aggressiveness, metastasis, and resistance to chemotherapy, leading to poor clinical outcomes. Targeted drug delivery nanoparticles can significantly reduce off-target toxicity of chemotherapy by selectively targeting tumor tissues. Polymersomes are self-assembled drug-encapsulated polymeric nanoparticles in which an aqueous core is enclosed by a bilayer membrane. To attain the appropriate therapeutic efficacy, polymersomes need to rapidly release their anticancer drug at the tumor sites. To fulfill this requirement, stimuli-responsive polymersomes have been developed. Since most of the tumors have hypoxic areas inside, hypoxia-responsive polymersomes are one of the most effective drug delivery vehicles for cancer treatment. To prepare targeted drug delivery systems, functionalizing polymersomes with specific ligands intended to be recognized by the receptors of the cancer cells, is the most common strategy. Herein, we designed three distinct hypoxia-responsive polymersomes for targeting breast cancer tissues. More than 80% of breast cancers express estrogen receptor (ER-positive), and about 15-25% of them do not express any receptors (triple-negative). Hence, we decorated our polymersomes with three different ligands including estradiol and endoxifen for targeting ER-positive breast microtumors, and iRGD peptide for targeting triple-negative breast tumors.