This proposal was received in response to Nanoscale Science and Engineering initiative, NSF 05-610, category NIRT. The objective of this research is to construct hybrid stimuli-responsive nanoparticles for controlled delivery of bioactive agents. The approach is to: i) fabricate porous nanoparticles made of gold, silica or composites thereof grafted with genetically engineered stimuli-sensitive polymers and ii) evaluate biomolecule loading, diffusion, and release from the nanoconstructs as a function of environmental conditions (pH, temperature).
Controlled drug delivery systems traditionally use chemically synthesized polymer-based materials. Control over polymer structure is a major challenge, which affects their ability to carry and release drugs in the body. There is a clear need to develop advanced systems with a higher degree of control over their ability to release the therapeutic payload in a predictable manner. The current research proposes the fabrication of hybrid inorganic porous nanoparticles with "on-off" pore caps on their surface made of thermal and pH - responsive recombinant polymers. At body temperature and neutral pH of the blood stream the polymers will be collapsed over the particle pores preventing drug release. In the decreased pH environment (such as that in and around a tumor) the polymers will be solubilized, allowing drug release.
Broader Impacts:
These hybrid nanostructures provide the benefit of robust inorganic cores on one hand where their size and porosity do not change in biological environments, and the flexible surface grafted polymers on the other allowing controlled drug release. The nanoplatforms can be broadly applied in delivery, sensing, separation, diagnostics and other areas where smart materials are utilized. The educational component of this project will facilitate training of new generations of students and scientists who will be able to work at the interface of basic and applied sciences for the design of novel nanoconstructs for use in biomedical applications.
