Biomaterial Drones for Image-Guided Drug Delivery during radiotherapy

用于放射治疗期间图像引导药物输送的生物材料无人机

• 批准号: 10594527
• 负责人: Wilfred Ngwa
• 金额: $ 58.49万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10594527
• 关键词: Animal Model; Animals; Biocompatible Materials; Biodistribution; Cancer Patient; Cessation of life; Clinical; Clinical Trials; Collaborations; Consensus; Data; Development; Devices; Disease; Drug Administration Routes; Drug Delivery Systems; Drug usage; Ensure; Four-dimensional; Gadolinium; Goals; Hematology; Histopathology; Image; Immunologic Adjuvants; Immunotherapy; Implant; In Situ; Lung Neoplasms; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of lung; Maximum Tolerated Dose; Measures; Modeling; Monitor; Neoplasm Metastasis; Outcome Measure; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Photons; Polymers; Protocols documentation; Publishing; Quality of life; Radiation Oncology; Radiation therapy; Renal function; Safety; Scientist; Technology; Testing; Texture; Therapeutic; Therapeutic Index; Time; Toxic effect; Treatment Efficacy; Treatment outcome; Visualization; Weight; Work; X-Ray Computed Tomography; base; biodegradable polymer; biomaterial development; cancer care; cell killing; clinical translation; contrast imaging; design; drug distribution; experimental study; image guided; image guided radiation therapy; image guided therapy; image-guided drug delivery; imaging platform; immunotoxicity; industry partner; innovation; intravenous administration; intravenous injection; nanoparticle; new technology; novel; prototype; routine therapy; technology development; therapy outcome; treatment planning; treatment response; tumor; x-ray irradiation

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.

项目摘要 放疗是癌症护理的关键组成部分，用于治疗超过50％ 癌症患者。接受图像引导放射疗法的患者常规有惰性 放疗生物材料植入其肿瘤中。这些惰性的单一功能 生物材料是确保治疗过程中的几何准确性。鉴于这些惰性 生物材料已经如此不受限制地进入肿瘤子体积，有令人信服的 将这些单个功能惰性生物材料升级到多功能或“智能”的理由 这可以带来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用于图像的生物材料无人机的开发 免疫辅助的指导输送可以大大提高局部和转移性 肿瘤以最小的全身性或重叠毒性杀死。我们的初步研究已经 开发并测试了我们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死。我们将基于这些初步结果以优化 并确定可视化和定量4维分布的能力 免疫辅助药物有效载荷。使用无人机进行图像引导的主要优势 药物输送包括以下内容：1）无人机可以采用无额外 给癌症患者带来不便，因为他们只会替代当前使用的惰性 生物材料； 2）使用无人机的原位控制药物的原位输送将允许直接交付 肿瘤，显着最大程度地减少全身/重叠毒性，目前是关键的 具有竞争方法的障碍。 3）持续释放和肿瘤内生物分布 可以对药物有效载荷进行可视化和自定义，以实现出色的治疗功效； 4） 无人机设计允许加载不同的治疗有效载荷。这个特定的目的 项目将着重于与固有计算的纳米颗粒合并 层析成像（CT）和磁共振成像（MRI）的对比度，用于可视化和 分布的量化。这项技术的成功开发可以改变 放疗，允许使用该技术将放疗和免疫疗法结合在 一种智能设备，以增加局部或转移性疾病患者的治疗结果。 因为，转移造成超过90％的癌症死亡和痛苦，许多癌症 患者将受益于这项新技术。图像指导能力也将允许 用于治疗计划和促进临床所需的治疗反应监测 翻译。

项目成果

Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB).

• DOI: 10.3390/pharmaceutics15122778
• 发表时间: 2023-12-14
• 期刊: Pharmaceutics
• 影响因子: 5.4
• 作者: Moreau M;Acter S;Ngema LM;Bih N;Sy G;Keno LS;Chow KF;Sajo E;Nebangwa O;Walker J;Oh P;Broyles E;Ngwa W;Yasmin-Karim S
• 通讯作者: Yasmin-Karim S

Modelling treatment-response rates.

• DOI: 10.1038/s41551-021-00717-w
• 发表时间: 2021-04
• 期刊: Nature biomedical engineering
• 影响因子: 28.1
• 作者: Grassberger C;Ngwa W
• 通讯作者: Ngwa W

Cancer and COVID-19 Experiences at African Cancer Centers: The Silver Lining.

• DOI: 10.1200/go.20.00564
• 发表时间: 2021-03
• 期刊: JCO global oncology
• 影响因子: 4.5
• 作者: Grossheim L;Ruff P;Ngoma T;Vanderpuye V;Mwango G;Ochieng P;Palmer D;Kouya F;Lasebikan N;Ntekim A;Ngoma M;Bih N;Malloum A;Elzawawy A;Kerr D;Ngwa W
• 通讯作者: Ngwa W

Smart Radiotherapy Biomaterials for Image-Guided In Situ Cancer Vaccination.

• DOI: 10.3390/nano13121844
• 发表时间: 2023-06-12
• 期刊: NANOMATERIALS
• 影响因子: 5.3
• 作者: Ainsworth, Victoria;Moreau, Michele;Guthier, Romy;Zegeye, Ysaac;Kozono, David;Swanson, William;Jandel, Marian;Oh, Philmo;Quon, Harry;Hobbs, Robert F.;Yasmin-Karim, Sayeda;Sajo, Erno;Ngwa, Wilfred
• 通讯作者: Ngwa, Wilfred

Phytoradiotherapy: An Integrative Approach to Cancer Treatment by Combining Radiotherapy With Phytomedicines.

• DOI: 10.3389/fonc.2020.624663
• 发表时间: 2020
• 期刊: Frontiers in oncology
• 影响因子: 4.7
• 作者: Alfonzetti T;Yasmin-Karim S;Ngwa W;Avery S
• 通讯作者: Avery S