Biomaterial Drones for Image-Guided Drug Delivery during radiotherapy

项目摘要 放射治疗是癌症护理的重要组成部分，用于治疗超过50%的癌症患者。 癌症患者。接受图像引导放射治疗的患者常规具有惰性 放射治疗生物材料植入他们的肿瘤。这些惰性物质的单一功能 生物材料是为了确保治疗过程中的几何精度。鉴于这些惰性的 生物材料已经可以不受限制地进入肿瘤子体积，这是令人信服的。 将这些单一功能的惰性生物材料升级为多功能或“智能”生物材料的理由 其可以提供额外的治疗或治疗增强益处。为此中央 该项目的创新和总体目标是开发生物材料无人机，用于图像- 可显著增强局部和转移性免疫佐剂的引导递送 以最小的全身毒性或重叠毒性杀死肿瘤。我们的初步研究已经 开发并测试了我们的生物材料无人机原型，表明它们确实可以 增强局部和转移性肿瘤细胞杀伤。我们将在这些初步结果的基础上， 并建立可视化和量化四维分布的能力， 免疫佐剂药物有效载荷。使用无人机进行图像制导的主要优点 药物递送包括以下内容：1）无人机可以在没有额外费用的情况下使用 癌症患者的不便，因为它们将简单地取代目前使用的惰性 生物材料; 2）使用无人机的药物原位受控递送将允许直接递送到 肿瘤，显着减少全身/重叠毒性，这是目前的关键 与竞争的方法的障碍。3)的持续释放和肿瘤内生物分布 药物有效载荷可以可视化和定制，以实现上级治疗功效; 4） 无人机设计允许装载不同的治疗有效载荷。具体目标是 该项目将侧重于将载药纳米颗粒与固有的计算 断层扫描（CT）和磁共振成像（MRI）造影剂用于可视化， 分布的量化。这项技术的成功开发可以改变 放射治疗，允许使用该技术将联合收割机和免疫治疗结合起来， 一个智能设备，以提高局部或转移性疾病患者的治疗效果。 因为，转移是负责超过90%的癌症死亡和痛苦，许多癌症 患者将受益于这项新技术。图像引导能力还将允许 用于治疗计划和治疗反应监测，以促进临床 翻译.

Project Summary Radiotherapy is a crucial component of cancer care, employed in the treatment of over 50% of cancer patients. Patients undergoing image-guided radiotherapy routinely have inert radiotherapy biomaterials implanted into their tumors. The single function of these inert biomaterials is to ensure geometric accuracy during treatment. Given that these inert biomaterials already have such unfettered access to the tumor sub-volume, there is compelling rationale for upgrading those single function inert biomaterials to multifunctional or `smart' ones that can deliver additional therapeutic or treatment enhancing benefits. To this end, the central innovation and overall goal of this project is the development of Biomaterial drones for image- guided delivery of immunoadjuvants which can substantially boost both local and metastatic tumor kill with minimal systemic or overlapping toxicities. Our preliminary studies have already developed and tested the prototypes of our biomaterial drones, showing that they can indeed boost local and metastatic tumor cell kill. We will build on these preliminary results to optimize and establish capability for visualization and quantification of the 4 dimensional distribution of the immunoadjuvant drug payload. Major advantages of employing the drones for image-guided drug delivery include the following: 1) the drones can be employed at no additional inconvenience to cancer patients, since they would simply replace currently used inert biomaterials; 2) controlled in situ delivery of drugs using drones will allow direct delivery to the tumor, significantly minimizing systemic/overlapping toxicities, which are currently a critical barrier with competing approaches. 3) the sustained release and intra-tumor bio-distribution of drug payloads can be visualized and customized to enable superior therapeutic efficacy; 4) the drones design allows for loading of different therapeutic payloads. The specific aims of this project will focus on incorporating drug-loaded nanoparticles with inherent computed tomography (CT) and magnetic resonance imaging (MRI) contrast for visualization and quantification of distribution. Successful development of this technology could transform radiotherapy, allowing the use of the technology to combine radiotherapy and immunotherapy in one smart device, to boost treatment outcomes for patients with local or metastatic disease. Because, metastasis is responsible for over 90% of cancer deaths and suffering, many cancer patients would benefit from this new technology. The image guidance capability will also allow for treatment planning, and treatment response monitoring needed for facilitating clinical translation.