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A DNA-mediated crosslinking strategy to enhance cellular delivery and sensor performance of protein spherical nucleic acids
Authors:Jing Yan  Ya-Ling Tan  Min-jie Lin  Hang Xing  Jian-Hui Jiang
Affiliation:Institute of Chemical Biology and Nanomedicine, Hunan University, Changsha 410082 P. R. China.; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082 P. R. China
Abstract:Intracellular delivery of enzymes is essential for protein-based diagnostic and therapeutic applications. Protein-spherical nucleic acids (ProSNAs) defined by protein core and dense shell of oligonucleotides have been demonstrated as a promising vehicle-free enzyme delivery platform. In this work, we reported a crosslinking strategy to vastly improve both delivery efficiency and intracellular sensor performance of ProSNA. By assembling individual ProSNA with lactate oxidase (LOX) core into a nanoscale particle, termed as crosslinked SNA (X-SNA), the enzyme delivery efficiency increased up to 5–6 times higher. The LOX X-SNA was later demonstrated as a ratiometric probe for quantitative detection of lactate in living cells. More importantly, X-SNA probe showed significantly improved sensor performance with signal-to-noise ratio 4 times as high as ProSNA when detecting intracellular lactate.

By crosslinking protein spherical nucleic acid (SNA) into a supramolecular architecture X-SNA, the intracellular enzyme delivery efficiency was significantly enhanced, showing 3–4 times higher signal-to-noise ratio in detecting intracellular lactate.
Keywords:
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