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。接受影像引导放射治疗的患者通常有惰性 放射治疗生物材料植入他们的肿瘤。这些惰性物质单一功能 生物材料是为了确保治疗过程中的几何精度。鉴于这些惰性物质 生物材料已经无拘无束地获得了肿瘤的子体积，有令人信服的 将单功能惰性生物材料升级为多功能或智能生物材料的理由 这可以提供额外的治疗或治疗增强的好处。为此，中央 该项目的创新点和总体目标是研制用于成像的生物材料无人机- 可显著促进局部和转移的免疫佐剂的引导递送 以最小的全身性或重叠毒性杀死肿瘤。我们的初步研究已经 开发和测试了我们的生物材料无人机的原型，表明它们确实可以 增强局部和转移性肿瘤细胞杀伤力。我们将在这些初步结果的基础上优化 并建立可视化和量化4维分布的能力 免疫佐剂药物的有效载荷。使用无人机进行图像制导的主要优势 药物输送包括以下几个方面：1)无人机可以在不增加额外费用的情况下使用 给癌症患者带来不便，因为他们只需更换目前使用的惰性物质 生物材料；2)使用无人机控制的就地药物输送将允许直接将药物输送到 肿瘤，显著减少全身性/重叠毒性，这是目前至关重要的 用相互竞争的方法设置障碍。3)缓释制剂及其在肿瘤内的生物分布 药物有效载荷可以可视化和定制，以实现卓越的治疗效果；4) 无人机的设计允许装载不同的治疗有效载荷。这样做的具体目的是 该项目将专注于将载药纳米颗粒与固有的计算机 体层摄影术(CT)和磁共振成像(MRI)对比度用于可视化和 分配的量化。这项技术的成功开发可能会改变 放射治疗，允许使用该技术将放射治疗和免疫治疗结合在一起 一种智能设备，用于提高局部或转移性疾病患者的治疗结果。 因为，转移是超过90%的癌症死亡和痛苦的原因，许多癌症 患者将从这项新技术中受益。图像制导能力还将允许 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.