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Full-Text Articles in Engineering

Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter Jul 2020

Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter

Doctoral Dissertations

Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of …


Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das Mar 2020

Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das

Doctoral Dissertations

Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …


Investigation On Nanoparticle Based Combination Therapy For Targeted Cancer Treatment, Muhammad Raisul Abedin Jan 2020

Investigation On Nanoparticle Based Combination Therapy For Targeted Cancer Treatment, Muhammad Raisul Abedin

Doctoral Dissertations

“The current treatment methods in cancer are associated with toxicity in healthy tissues, partial therapeutic response, drug resistance and finally recurrence of the disease. The cancer drugs are challenged by non-specific binding, undesired toxicity in healthy cells, low therapeutic index and finally poor therapeutic outcome. In this work, a targeted nanoscale therapeutic system Antibody Drug Nanoparticle (ADN) was engineered to selectively inhibit the breast cancer cell growth with reduced toxicity in healthy cells. The ADNs were designed by synthesizing rod shaped anoparticles using pure chemotherapeutic drug and covalently conjugating a therapeutic monoclonal antibody (mAb) on the surface of the drug …


Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley Dec 2016

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …


Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen Jul 2016

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …


Design Of A Targeted Bacterial Drug Delivery Vector For The Treatment Of Cancer And Metastases, Charles Alexander Swofford Aug 2014

Design Of A Targeted Bacterial Drug Delivery Vector For The Treatment Of Cancer And Metastases, Charles Alexander Swofford

Doctoral Dissertations

Engineered Salmonella possess unique capabilities that make them ideal drug delivery vectors for tumors. Targeted bacterial delivery of anticancer proteins has the ability to overcome therapeutic resistance in tumors that limits the efficacy of chemotherapeutics. In my doctoral research, I identified a protein-drug that can be expressed by bacteria and rapidly kills cancer cells. I also created a density dependent switch that initiates gene expression in tumors and prevents expression in healthy tissue. Combining these two systems has created a potent anti-cancer system that targets tumors with minimal toxicity. I cloned genes for five potential anti-cancer proteins into Salmonella. …