Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer
Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer
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DOI：
10.1073/pnas.1121174109
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发表时间：
2012-07-31
影响因子：
11.1
通讯作者：
Katti, Kattesh V.
中科院分区：
文献类型：
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作者：
Shukla, Ravi;Chanda, Nripen;Katti, Kattesh V.
治疗药物对实体肿瘤的全身输送受到血管和间质屏障的阻碍。我们假设，前列腺癌特异性表儿茶素没食子酸酯(EGCG)功能化放射性金纳米颗粒，当肿瘤内(IT)，将绕过运输障碍，导致靶向输送治疗有效载荷。这里描述的结果支持我们的假设。我们报道了从Au-198同位素衍生的固有治疗性金纳米颗粒的开发；Au-198β颗粒(组织中约11毫米或约1100个细胞直径)的范围足够长，足以提供向前列腺内细胞传递的辐射剂量的交叉火力效应，而足够短，足以将对胶囊外围附近关键组织的辐射剂量降至最低。生物相容(198)AuNPs的配方利用了前列腺癌特异性植物化学物质EGCG的氧化还原化学，因为它将金盐转化为金纳米颗粒，并与在前列腺肿瘤细胞中过度表达的Laminin67R受体选择性结合。在PC-3异种移植SCID小鼠体内的药代动力学研究表明，瘤内给药24小时后，(AuNP)-Au-198-EGCG在肿瘤中的保留率约为72%。治疗研究显示，与对照组相比，28天后肿瘤体积缩小了80%，显示出明显的肿瘤生长抑制。这种创新的纳米技术方法是设计生物相容的靶向特定抗肿瘤药物的基础。这种新型的肿瘤内可注射(AuNP)-Au-198-EGCG纳米治疗剂可能在肿瘤学方面取得重大进展，用于前列腺癌和其他实体肿瘤的有效治疗。
Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the Au-198 beta-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of bio-compatible (198)AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of (AuNP)-Au-198-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable (AuNP)-Au-198-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.