Development of polyphenolic nanoparticles for biomedical applications.

摘要

Polymeric nanoparticles have a wide range of applications, particularly as drug delivery and diagnostic agents, and tannins have been regarded as a promising building block for redox and pH responsive systems. Tannins are a class of naturally occurring polyphenols commonly produced by plants and are found in many of our consumables like teas, spices, fresh fruits, and vegetables. Many of the health benefits associated with these foods are a result of their high tannin contents and the many different types of tannins found in various plants have demonstrated therapeutic potentials for conditions ranging from cardiovascular disease and diabetes to ulcers and cancer. Diets rich in tannins have been associated with lower blood pressure in patients with hypertension. The plurality of phenols in tannins also makes them powerful antioxidants and as a result, there is a lot of interest in taking advantage of their self-assembling abilities to make redox and pH responsive drug delivery systems. However, the benefit of natural tannins is limited by their instability in physiological conditions. Furthermore, there is limited control over molecular weight and reactivity of the phenolic content of plant extracts. Herein we report the novel synthesis of pseudotannins with control over molecular weight and reactivity of phenolic moieties. These pseudotannins have can form nanoscale interpolymer complexes under physiological conditions and have demonstrated antioxidative potential. Furthermore, pseudotannin IPCs have been shown to be responsive to physiologically relevant oxidation as well as the ability to easily incorporate cell targeting peptides, fluorescent tags, and MRI contrast agents. The work presented here describes how pseudotannins would be ideally suited to minimally invasive techniques for diagnosing atherosclerotic plaques and targeting triple negative breast cancer. We demonstrate that pseudotannin can very easily and quickly form nanoscale particles that are small enough to be uptaken into mammalian cells. Furthermore, by self-assembling with gadolinium, pseudotannins can effectively attenuate the signal of gadolinium based MRI contrast agents. This in conjunction with oxidation responsive decomplexation could be a viable option for diagnosing the severity and risk of rupture of atherosclerotic plaques. Also, we demonstrate that pegylated compounds can easily be incorporated into pseudotannin nanoparticles to impart cell targeting functionality. The subsequent uptake of pseudotannin nanoparticles into breast cancer cells demonstrated the ability to increase their sensitivity to UV radiation. The creation of synthetic tannin-like polymers leads to directly to making a variety of self-assembling, stimuli responsive, and bioactive nanoparticles well-suited for various biomedical applications.