Radiotherapeutic Nanoseeds for Internal Radiation Therapy of Unresectable Solid Tumors

项目总结 如果恶性肿瘤附着在重要结构或手术上，则被认为是“无法切除的”。 会对患者造成不可逆转的损害，并损害他们的生活质量。这种实体瘤可以 起源于各种类型的癌症，包括前列腺癌、肺癌、结肠癌、胰腺癌、肝癌、卵巢癌、头皮癌和 脖子，还有其他的。此外，对于转移性癌症患者，切除可能会造成相当大的损失。 发病率，因为他们已经被转移的疾病、化疗和/或 放射疗法。为了防止肿瘤生长或提供完全的肿瘤解决方案 外科手术、各种细胞毒药物和放射疗法目前都在临床实践中。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 情况黯淡，存活率仍然很低。这个项目的目标是开发一种临床实用的 内放射治疗对不能切除的实体瘤的更有效的治疗 减少不良副作用。 最近，我们开发了一种制备中空金纳米颗粒的合成工艺 核/壳结构，可直接转化为独特的金属放射性标记方法 纳米平台将被用作癌症的放射治疗剂。我们加入了钯-103(103Pd)， 一种目前在临床上进行近距离放射治疗的放射性同位素，变成一个中空的金纳米颗粒。由此产生的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， 作为放射治疗的内放射源(纳米种子)。纳米种子的大小， 直径约150 nm，大到足以防止纳米种子在仍然很小的情况下扩散到其他区域 足以让它们均匀地分布在肿瘤内。我们进一步进行了初步的 103Pd@Au纳米种子瘤内注射治疗效果的实验研究 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担减轻 与对照组相比提高了80%。鉴于这些治疗剂的前景广阔， 通过我们的初步研究，我们建议进一步优化和测试这项技术，使其走向临床。 申请。如果成功，它将开启基于纳米种子的内辐射的许多可能的应用 治疗，有可能为无法切除的实体肿瘤提供另一种治疗方式 显著降低了副作用。

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.