A DNA-mediated crosslinking strategy to enhance cellular delivery and sensor performance of protein spherical nucleic acids

• Published in: Chemical science (Cambridge) Vol. 12; no. 5; pp. 183 - 189
• Main Authors: Yan, Jing, Tan, Ya-Ling, Lin, Min-jie, Xing, Hang, Jiang, Jian-Hui
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 08.12.2020; The Royal Society of Chemistry
• Subjects: Chemistry; Crosslinking; Diagnostic software; Diagnostic systems; Enzymes; Liquid oxygen; Nucleic acids; Oligonucleotides; Proteins; Sensors; Signal to noise ratio
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d0sc04977h

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.