MSN-on-a-Chip: Cell-Based Screenings Made Possible on a Small-Molecule Microarray of Native Natural Products

Bo Peng, Changmin Yu, Shubo Du, Si S. Liew, Xin Mao, Peiyan Yuan, Zhenkun Na, Shao Q. Yao

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)986-996
Number of pages11
JournalChemBioChem
Volume19
Issue number9
DOIs
Publication statusPublished - 4 May 2018
Externally publishedYes

Keywords

  • high-content screening
  • mesoporous silica nanoparticles
  • microarrays
  • natural products
  • phenotypic screening

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