PNAS：纳米金结合茶叶化合物治疗前列腺癌效果显著

近日，美国密苏里大学的科研人员发现了一种有效的前列腺癌治疗方式，能够借助放射性纳米金和在茶叶内发现的化合物“瞄准”前列腺肿瘤，并且不会损害病患体内的健康器官或影响其身体的正常机能。相关研究报告发表在美国《国家科学院学报》（PNAS）上。

研究中，科学家在茶叶中发现了一种能够被吸引至前列腺肿瘤细胞的特殊化合物。当将这种化合物与由研究反应堆产生的纳米金相结合时，茶叶内的化合物会帮忙将纳米粒子“传送”到肿瘤的所在区域，使得这些治疗性的临床级放射性同位素能够有效地破坏肿瘤细胞。

大多数时候，前列腺癌都发展得十分缓慢，但极具侵略性的前列腺癌却能快速蔓延至身体的其他部分。传统疗法需要将数百个放射性“种子”注射进前列腺，但这对极具侵略性的前列腺癌并无效果。“种子”的大小和它们传送有效剂量的能力受限，都会影响其对于前列腺癌的治疗。

而在新疗法中，每个纳米金都大小合适，只需要1次至2次注射，纳米粒子便会聚集在肿瘤内部，从而有望达到良好的治疗效果。研究人员坚信，放射性纳米金能够同时缩小缓慢生长和极具侵略性的前列腺肿瘤，甚至完全根除它们。这是因为纳米金不仅具有适合的尺寸，还具备很短的半衰期。其半衰期仅为2.7天，这意味着纳米金的放射将在3周内结束，因此能令纳米粒子保持较高的效力，使得肿瘤的体积能在28天治疗后大幅减小。

目前，研究小组已经在小鼠身上进行了测试，下一步还将在前列腺癌形态与人类十分接近的犬类身上进行测试，并逐步将测试拓展至大型动物和人体。

doi:10.1073/pnas.1121174109
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Laminin receptor specific therapeutic gold nanoparticles (¹⁹⁸AuNP-EGCg) show efficacy in treating prostate cancer

Ravi Shukla, Nripen Chanda, Ajit Zambre, Anandhi Upendran, Kavita Katti, Rajesh R. Kulkarni, Satish Kumar Nune, Stan W. Casteele, Charles Jeffrey Smith, Jatin Vimalh, Evan Boote, J. David Robertson, Para Kani, Hendrik Engelbrechtg, Lisa D. Watkinson, Terry L. Carmack, John R. Leverj, Cathy S. Cutler, Charles Caldwell, Raghuraman Kannan, and Kattesh V. Katti

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 ¹⁹⁸Au β-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 biocompatible ¹⁹⁸AuNPs 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 198AuNP-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 ¹⁹⁸AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.