Department of Chemistry, National University of Singapore, 3 Science Drive, Singapore, 117543, Singapore.
Institute of Advanced Materials (IAM), Nanjing Tech University, 30 South Puzhu Road, Nanjing, 21816, China.
Chembiochem. 2018 May 4;19(9):986-996. doi: 10.1002/cbic.201800101. Epub 2018 Apr 17.
Standard small-molecule microarrays (SMMs) are not well-suited for cell-based screening assays. Of the few attempts made thus far to render SMMs cell-compatible, all encountered major limitations. Here we report the first mesoporous silica nanoparticle (MSN)-on-a-chip platform capable of allowing high-throughput cell-based screening to be conducted on SMMs. By making use of a glass surface on which hundreds of MSNs, each encapsulated with a different native natural product, were immobilized in spatially defined manner, followed by on-chip mammalian cell growth and on-demand compound release, high-content screening was successfully carried out with readily available phenotypic detection methods. By combining this new MSN-on-a-chip system with small interfering RNA technology for the first time, we discovered that (+)-usniacin possesses synergistic inhibitory properties similar to those of olaparib (an FDA-approved drug) in BRCA1-knockdown cancer cells.
标准小分子微阵列（SMMs）不太适合基于细胞的筛选测定。迄今为止，为使 SMMs 与细胞兼容而进行的少数尝试都遇到了重大限制。在这里，我们报告了第一个介孔硅纳米粒子（MSN）在芯片上的平台，该平台能够在 SMMs 上进行高通量基于细胞的筛选。通过利用玻璃表面，数百个 MSN 被固定在空间上，每个 MSN 都封装有不同的天然产物，然后在芯片上进行哺乳动物细胞生长和按需化合物释放，成功地进行了高内涵筛选，并采用了现成的表型检测方法。通过首次将这种新型 MSN 芯片系统与小干扰 RNA 技术相结合，我们发现（+）-usniacin 具有与奥拉帕利（一种 FDA 批准的药物）相似的协同抑制特性，在 BRCA1 敲低的癌细胞中。
