Radiotherapeutic Nanoseeds for Internal Radiation Therapy of Unresectable Solid Tumors

用于不可切除实体瘤内放射治疗的放射治疗纳米种子

• 批准号: 9171891
• 负责人: Yaowu Hao
• 金额: $ 46.09万
• 依托单位: UNIVERSITY OF TEXAS ARLINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9171891
• 关键词: Adverse effects; Animals; Area; Brachytherapy; Brain Neoplasms; Caliber; Cancer Patient; Clinical; Colon; Control Groups; Cytotoxic agent; Diffuse; Disease; Disseminated Malignant Neoplasm; Dissociation; Electrolytes; Electron Microscopy; Evaluation; Excision; Glioblastoma; Glioma; Goals; Gold; Head and neck structure; Health; Image; In Vitro; Infusion procedures; Injection of therapeutic agent; Investigation; Isotopes; Knowledge; Liver; Lung; Magnetic Resonance Imaging; Magnetic nanoparticles; Magnetism; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Medicine; Metals; Methodology; Methods; Mission; Modality; Modeling; Monitor; Morbidity - disease rate; Neoplasm Metastasis; Operative Surgical Procedures; Ovarian; PC3 cell line; Palladium 103; Pancreas; Particle Size; Patients; Process; Prostate; Protocols documentation; Publishing; Quality of life; Radiation therapy; Radioisotopes; Radiolabeled; Radiometry; Rattus; Reporting; Research; Resolution; Solid Neoplasm; Source; Structure; Sulfhydryl Compounds; Surface; Survival Rate; Suspension substance; Suspensions; Technology; Testing; Therapeutic; Therapeutic Agents; Tissues; Translating; Treatment Efficacy; Tumor Burden; United States National Institutes of Health; Unresectable; X-Ray Computed Tomography; Xenograft Model; base; burden of illness; cancer type; chemotherapy; clinical application; clinical practice; cohort; contrast imaging; cytotoxic radiation; image visualization; imaging modality; improved; in vivo; internal radiation; iron oxide; microscopic imaging; nanoparticle; operation; prevent; radiotracer; research study; single photon emission computed tomography; tumor; tumor growth

PROJECT SUMMARY Malignant tumors are considered “unresectable” if they are adhere to vital structures or the surgery would cause irreversible damages to the patients and impair their quality of life. Such solid tumors can arise from a variety of cancer types including prostate, lung, colon, pancreatic, liver, ovarian, head and neck, and others. Also, for patients with metastatic cancers, the resection may cause considerable morbidity since they have already been weakened by their metastatic diseases, chemotherapy, and/or radiation therapy. In order to prevent the tumor growth or provide complete tumor resolution without surgery, a variety of cytotoxic drugs and radiation therapies are currently in clinical practice. Unfortunately, severe adverse side effects are usually associated with these therapeutic modalities. Since these tumors are already locally advanced or have begun to metastasize, the outlook today for these cancer patients is bleak and survival rate remains very low. The goal of this project is to develop a clinically practical internal radiation therapy for more efficient treatment of unresectable solid tumor cancers with significant reduction of adverse side effects. Recently, we have developed a synthesis process to produce hollow gold nanoparticle-based core/shell structures, which can be directly translated into a unique radiolabeling methodology for metal nanoplatforms to be used as radiotherapeutic agents of cancer. We incorporated palladium-103 (103Pd), a radioisotope currently in clinical brachytherapy, into a hollow gold nanoparticle. The resulting 103Pd@Au nanoparticles in the form of a colloidal suspension can be administered by direct injection into tumors, serving as internal radiation sources (nanoseeds) for radiation therapy. The size of the nanoseed, ~150nm in diameter, is large enough to prevent nanoseeds from diffusing into other areas while still small enough to allow them to homogeneously distribute inside the tumor. We further performed a preliminary experiment to test the therapeutic efficacy of 103Pd@Au nanoseeds when intratumorally injected into a prostate cancer (PCa) xenograft model. Remarkably, we observed an averaged tumor burden reduction of 80% as compared to control groups. Given the promising potential of such therapeutic agents shown by our preliminary, we propose here to further optimize and test this technology towards its clinical application. If successful, it will open up many possible applications of nanoseed-based internal radiation therapy, potentially providing an alternative therapeutic modality for unresectable solid tumors with significantly reduced side effects.

项目摘要 如果恶性肿瘤粘附在重要结构或手术部位， 会对病人造成不可逆转的损害，影响他们的生活质素。这种实体瘤可以 由多种癌症类型引起，包括前列腺癌、肺癌、结肠癌、胰腺癌、肝癌、卵巢癌、脑癌和 脖子和其他。此外，对于转移性癌症患者，切除术可能会导致相当大的 发病率，因为他们已经被他们的转移性疾病，化疗，和/或 放射治疗为了防止肿瘤生长或提供完全的肿瘤消退， 外科手术、各种细胞毒性药物和放射疗法目前在临床实践中。不幸的是， 严重的副作用通常与这些治疗方式有关。因为这些肿瘤 已经局部晚期或已经开始转移，这些癌症患者今天的前景 生存率仍然很低。该项目的目标是开发一种临床实用的 内放射治疗可更有效地治疗不可切除的实体瘤癌症， 减少不良副作用。 最近，我们开发了一种合成工艺来生产基于空心金纳米颗粒的 核/壳结构，可以直接转化为金属的独特放射性标记方法 纳米平台可用作癌症的放射治疗剂。我们将钯-103（103 Pd）， 一种目前用于临床近距离放射治疗的放射性同位素，放入一个中空的金纳米颗粒中。生成的103Pd@Au 胶体悬浮液形式的纳米颗粒可以通过直接注射到肿瘤中来给药， 用作放射治疗的内部放射源（纳米粒子）。纳米种子的大小， 直径约150 nm，足够大，以防止纳米种子扩散到其他区域，同时仍然很小 足以使它们均匀分布在肿瘤内。我们进一步进行了初步的 实验以测试103Pd@Au纳米种子在肿瘤内注射到肿瘤中时的治疗功效。 前列腺癌（PCa）异种移植模型。值得注意的是，我们观察到平均肿瘤负荷减少 80%，与对照组相比。鉴于这种治疗剂显示出的有希望的潜力， 通过我们的初步研究，我们建议进一步优化和测试该技术以用于临床 应用程序.如果成功的话，它将为基于纳米种子的内部辐射开辟许多可能的应用 治疗，可能为不可切除的实体瘤提供替代治疗方式， 大大降低了副作用。