DNA-Functionalized Metal-Organic Framework Nanoparticles for Intracellular Delivery of Proteins

Shunzhi Wang, Yijing Chen, Shuya Wang, Peng Li, Chad A. Mirkin*, Omar K. Farha

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

Due to their large size, charged surfaces, and environmental sensitivity, proteins do not naturally cross cell-membranes in intact form and, therefore, are difficult to deliver for both diagnostic and therapeutic purposes. Based upon the observation that clustered oligonucleotides can naturally engage scavenger receptors that facilitate cellular transfection, nucleic acid-metal organic framework nanoparticle (MOF NP) conjugates have been designed and synthesized from NU-1000 and PCN-222/MOF-545, respectively, and phosphate-terminated oligonucleotides. They have been characterized structurally and with respect to their ability to enter mammalian cells. The MOFs act as protein hosts, and their densely functionalized, oligonucleotide-rich surfaces make them colloidally stable and ensure facile cellular entry. With insulin as a model protein, high loading and a 10-fold enhancement of cellular uptake (as compared to that of the native protein) were achieved. Importantly, this approach can be generalized to facilitate the delivery of a variety of proteins as biological probes or potential therapeutics.

Original languageEnglish (US)
Pages (from-to)2215-2219
Number of pages5
JournalJournal of the American Chemical Society
Volume141
Issue number6
DOIs
StatePublished - Feb 13 2019

ASJC Scopus subject areas

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

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