SBIR Topic 241 Phase II: Platelet-based Nanoparticle Therapy for Prostate Cancer

该II期提案的目标是开发用于成像、组织消融和释放针对前列腺癌脉管系统的治疗方式的定向能量转移方法。该平台技术是含有超顺磁性氧化铁（SPIO）纳米颗粒的冻干人血小板（Stasix颗粒）。I期项目表明，SPIO-Stasix颗粒选择性地定位于免疫功能低下小鼠宿主上的人前列腺异种移植物中受损的脉管系统。我们建议进一步验证使用载有氧化铁的人血小板产品作为成像和治疗方式的递送载体;使用噬菌体展示技术来增强人血小板纳米颗粒或合成微器件对前列腺癌微血管的靶向;证明靶向前列腺微血管的纳米器件可以启动前列腺的靶向热诱导损伤;并在临床试验中验证和测试前列腺癌患者中雄激素剥夺疗法诱导的治疗窗。该提案代表了将热疗和造影剂靶向、成像和递送至前列腺微血管作为前列腺癌治疗和诊断工具的完整表征。

The goal of this Phase II proposal is to develop directed energy transfer methods for imaging, tissue ablation and release of therapeutic modalities targeted to the vasculature of prostate cancer. The platform technology is a freeze-dried human platelet (Stasix particles) that contains super paramagnetic iron oxide (SPIO) nanoparticles. The Phase I program showed that SPIO-Stasix particles selectively localize to damaged vasculature in human prostate xenografts on immunocompromised mouse hosts. We propose to further validate the use of human platelet products loaded with iron oxides as delivery vehicles for imaging and therapeutic modalities; to use phage display technology to enhance the targeting of human platelet nanoparticles or synthetic microdevices to prostate cancer microvasculature; to demonstrate that nanodevices targeted to prostate microvasculature can initiate targeted heat-induced damage of the prostate; and to validate and test in clinical trials the therapeutic window induced by androgen deprivation therapy in prostate cancer patients. This proposal represents a full characterization of the targeting, imaging and delivery of heat therapy and contrast agents to prostate microvasculature as a tool for the treatment and diagnosis of prostate cancer.