Protein Spherical Nucleic Acids for Live-Cell Chemical Analysis

Devleena Samanta, Sasha B. Ebrahimi, Caroline D. Kusmierz, Ho Fung Cheng, Chad A. Mirkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


We report the development of a new strategy for the chemical analysis of live cells based on protein spherical nucleic acids (ProSNAs). The ProSNA architecture enables analyte detection via the highly programmable nucleic acid shell or a functional protein core. As a proof-of-concept, we use an i-motif as the nucleic acid recognition element to probe pH in living cells. By interfacing the i-motif with a forced-intercalation readout, we introduce a quencher-free approach that is resistant to false-positive signals, overcoming limitations associated with conventional fluorophore/quencher-based gold NanoFlares. Using glucose oxidase as a functional protein core, we show activity-based, amplified sensing of glucose. This enzymatic system affords greater than 100-fold fluorescence turn on in buffer, is selective for glucose in the presence of close analogs (i.e., glucose-6-phosphate), and can detect glucose above a threshold concentration of ∼5 μM, which enables the study of relative changes in intracellular glucose concentrations.

Original languageEnglish (US)
Pages (from-to)13350-13355
Number of pages6
JournalJournal of the American Chemical Society
Issue number31
StatePublished - Aug 5 2020

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry


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