Hollow porous silica nanoparticles for targeted drug delivery

描述（由申请人提供）：介孔二氧化硅基材料显示出许多对生物医学应用有吸引力的特征，例如稳定的介孔结构、大的表面积、可调的孔径和体积、良好的生物相容性以及可用于进一步功能化的明确的表面性质。本项目的目标是开发聚合物改性的中空多孔二氧化硅纳米粒子，具有可逆的药物释放控制，将适合于靶向药物递送。为了研究这些新型纳米粒子介导的递送系统的临床潜力，我们选择临床相关的抗肿瘤药物和前列腺肿瘤模型。我们将通过追求以下具体目标来实现本申请的总体目标：1.制备具有可逆pH控制药物释放的中空多孔二氧化硅（HPS）纳米粒。2.评价负载有热休克蛋白90（Hsp90）抑制剂17-AAG的HPS纳米颗粒的体外抗增殖作用和体内前列腺癌模型中的肿瘤抑制作用。我们预计，本提案中开发的新型HPS纳米颗粒将建立一个适用于各种生物医学应用的新药物递送平台。这些混合无机/有机纳米颗粒的设计灵活性特别适合于制备将在单一制剂中组合联合收割机多种功能，特别是成像和药物递送的系统。早期应用于临床相关问题将允许这种纳米技术平台快速发展到癌症治疗中的应用。这一提议的探索性质应非常适合21国责任供资机制。 项目简介：该项目涉及智能多孔纳米颗粒的设计，用于将药物靶向递送到前列腺肿瘤中。所提出的纳米颗粒被设计成选择性地在肿瘤细胞内打开它们的孔，并且应该在治疗各种癌症中找到应用。

DESCRIPTION (provided by applicant): 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.