miRNA-Specific Unlocking of Drug-Loaded Metal–Organic Framework Nanoparticles: Targeted Cytotoxicity toward Cancer Cells

Wei Hai Chen, Guo Feng Luo, Yang Sung Sohn, Rachel Nechushtai, Itamar Willner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

UiO-68 metal–organic framework nanoparticles (NMOFs) are loaded with a doxorubicin drug (fluorescent dye analogs) and locked by means of structurally engineered duplex nucleic acid structures, where one strand is covalently linked to the NMOFs and the second strand is hybridized with the anchor strand. Besides the complementarity of the second strand to the anchor sequence, it includes the complementary sequence to the microRNAs (miRNA)-21 or miRNA-221 that is specific miRNA biomarker for MCF-7 breast cancer cells or OVCAR-3 ovarian cancer cells. In the presence of the respective miRNA biomarkers, the miRNA-induced displacement of the strand associated with the anchor strand proceeds, resulting in the release of DNA/miRNA duplexes. The released duplexes are, however, engineered to be digested in the presence of exonuclease III, Exo III, a process that recycles the miRNAs and provides the autonomous amplified unlocking of the NMOFs and the release of the doxorubicin load (or the fluorescent dye analogs) even at low concentrations of miRNA. Preliminary cell experiments reveal that the respective NMOFs are unlocked by the miRNA-21 or miRNA-221, resulting in selective cytotoxicity toward MCF-7 breast cancer cells or OVCAR-3 ovarian cancer cells.

Original languageAmerican English
Article number1900935
JournalSmall
Volume15
Issue number17
DOIs
StatePublished - 26 Apr 2019

Bibliographical note

Publisher Copyright:
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

  • biomarkers
  • breast cancer
  • logic gate
  • miRNA-21
  • miRNA-221
  • ovarian cancer

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