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MSN‐on‐a‐Chip: Cell‐Based Screenings Made Possible on a Small‐Molecule Microarray of Native Natural Products
Author(s) -
Peng Bo,
Yu Changmin,
Du Shubo,
Liew Si S.,
Mao Xin,
Yuan Peiyan,
Na Zhenkun,
Yao Shao Q.
Publication year - 2018
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201800101
Subject(s) - small molecule , natural product , high throughput screening , nanotechnology , dna microarray , microarray , gene knockdown , chemistry , phenotypic screening , cell , computational biology , materials science , biology , gene , biochemistry , gene expression , phenotype
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.