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Research

 

Nanotechnology

Nanotechnology is the study of the fabrication, directed self-assembly, and characterization of materials that have size dimensions between 1 and 100 nanometers. In the context of biological nanostructures, this is the size regime of the molecular machinery that constitutes, for example, functional viruses, bacteria, and human cells. The challenge of bio-nanotechnology and the focus of The Thaxton Laboratory is to control the synthesis of structures that naturally interface with biological systems to develop exquisitely targeted, practical, safe, and effective nanoparticle therapeutics, imaging agents, and biosensors.
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BioMimetic High Density Lipoprotein Nanoparticles as Therapeutics for Atherosclerosis

My laboratory aims to develop nanotherapeutics for treating atherosclerosis, the disease mechanism responsible for heart attack and stroke. Atherosclerosis is systemic infiltrative and inflammatory disease of the arterial tree resulting from an excess of circulating cholesterol, in large part, carried by low density lipoproteins (LDL). HMG-CoA reductase inhibitors ('statins') reduce serum levels of LDL and cardiovascular disease risk. However, given the disease burden, novel therapeutics are needed to augment the benefits of statins. High density lipoproteins (HDL) are responsible for a process known as reverse cholesterol transport whereupon cholesterol is picked up by HDL from sites of pathologic accumulation (e.g. artery walls) and earmarked for excretion. By preventing and reversing damage done by cholesterol infiltration of arterial walls, HDL levels inversely correlate with cardiovascular disease risk.

Unfortunately, there are no robust therapeutic options for increasing serum HDL levels or that augment beneficial HDL function. My research group recently fabricated a novel nanoparticle version of mature spherical HDL that closely approximates the size, shape, and surface chemistry of naturally occurring HDL, and data demonstrates that the nanoparticle HDLs tightly bind cholesterol. Synthetic HDL nanoparticles were fabricated by using an inorganic gold nanoparticle (AuNP) core to template the overall size and shape of the HDL AuNPs, and to take advantage of favorable surface chemistry. Significant work is underway to understand the in vitro and in vivo biology of HDL AuNPs, and also to fabricate the next generation of HDL nanoparticles. By rationally tailoring the chemistry of fabricated HDL nanoparticles, we aim to determine important physicochemical and biological structure-function relationships that will translate into the next generation of therapeutics for atherosclerosis.
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BioMimetic High Density Lipoprotein Nanoparticles for Therapeutic Delivery

In addition to heart disease, some cancer cells express receptors for HDLs due to their increased need for cholesterol. Accordingly, HDL nanoparticles are being used as vehicles to deliver potent therapies to cancer cells that express HDL receptors.  One class of therapeutic molecules formulated with HDLs is the nucleic acids (e.g. antisense-DNAs, microRNAs, siRNAs, etc.). HDLs and HDL nanoparticles appear to be uniquely capable of binding, stabilizing, and delivering therapeutic nucleic acids to cells to regulate target gene expression. The Thaxton Lab is applying this concept and the HDL nanoparticles to many cancer types, including prostate cancer.
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Prostate Cancer and Nano-Diagnostics

Even with the most sophisticated commercial prostate specific antigen (PSA) blood tests, ‘undetectable’ is the answer provided most patients with regard to their PSA level after undergoing primary therapy for prostate cancer, as well as for many patients who are undergoing adjuvant and/or salvage therapy. For those patients who experience disease relapse, first heralded by a detectable and then rising PSA level, ‘undetectable’ provided false hope. Due to advances in nanotechnology, we are prepared to prospectively evaluate post-treatment PSA kinetics in order to provide the earliest and most accurate information to physicians and patients with regard to disease cure and recurrence. Accordingly, current and investigative treatments can be withheld in the case of disease cure. Furthermore, such treatments can be provided appropriately, and in a timely fashion, under the auspices of properly designed clinical trials while assessing biological (i.e. PSA) response to therapy.
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