The limited delivery of chemotherapy agents to cancer cells and the nonspecific action of these agents are significant challenges in oncology. We have previously developed a customizable drug delivery and activation system in which a nucleic acid functionalized gold nanoparticle (Au-NP) delivers a drug that is selectively activated within a cancer cell by the presence of an mRNA unique to the cancer cell. The amount of drug released from sequestration to the Au-NP is determined by both the presence and the abundance of the cancer cell specific mRNA in a cell. We have now developed this technology for the potent, but difficult to deliver, topoisomerase I inhibitor SN-38. Herein, we demonstrate both the efficient delivery and selective release of SN-38 from gold nanoparticles in Ewing sarcoma cells with resulting efficacy in vitro and in vivo. These results provide further preclinical validation for this novel cancer therapy and may be extendable to other cancers that exhibit sensitivity to topoisomerase I inhibitors.

中文翻译：

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尤因肉瘤特异性mRNA激活的SN-38共轭金纳米颗粒具有体外和体内功效。

化疗药物向癌细胞的有限递送和这些药物的非特异性作用是肿瘤学中的重大挑战。我们先前已经开发了可定制的药物输送和激活系统，其中核酸功能化的金纳米颗粒（Au-NP）输送通过癌细胞独特的mRNA存在而在癌细胞内选择性激活的药物。从螯合释放到Au-NP中释放的药物量由细胞中癌细胞特异性mRNA的存在和丰度决定。现在，我们已经针对强效但难以交付的拓扑异构酶I抑制剂SN-38开发了该技术。在本文中，我们证明了尤金肉瘤细胞中金纳米颗粒有效递送和选择性释放SN-38，并在体内和体外产生了功效。