Mesoporous silica-based materials show number of attractive features for biomedical applications, such as stable mesoporous structures, large surface areas, tunable pore sizes and volumes, good biocompatibility, and well-defined surface properties available for further functionalization. The objective of this project is to develop polymer-modified hollow porous silica nanoparticles with a reversible control of drug release that will be suitable for target-specific drug delivery. To examine the clinical potential of these novel nanoparticle-mediated delivery systems, we choose clinically relevant anti-tumor agent and prostate tumor model. We will accomplish the overall objectives of this application by pursuing the following specific aims: 1. Prepare hollow porous silica (HPS) nanoparticles with reversible pH-controlled drug release. 2. Evaluate anti-proliferative effect of the HPS nanoparticles loaded with 17-AAG, an inhibitor of heat shock protein 90 (Hsp90), in vitro and tumor inhibition in a prostate cancer model in vivo. We anticipate that the novel HPS nanoparticles developed in this proposal will establish a new drug delivery platform suitable for a variety of biomedical applications. The design flexibility of these hybrid inorganic/organic nanoparticles is particularly suitable for the preparation of systems that will combine multiple functions within a single formulation, in particular imaging and drug delivery. Early application to a clinically relevant problem will allow fast progression of this nanotechnology platform to application in cancer treatment. The exploratory nature of this proposal should be ideally suited for the R21 funding mechanism. ? ? Project Narrative: This project deals with the design of smart porous nanoparticles for targeted delivery of drugs into prostate tumors. The proposed nanoparticles are designed to open their pores selectively inside of tumor cells and should find application in the treatment of a wide range of cancers. ? ? ?
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