Stimuli-Responsive Nucleic Acid-Based Polyacrylamide Hydrogel-Coated Metal–Organic Framework Nanoparticles for Controlled Drug Release

Wei Hai Chen, Wei Ching Liao, Yang Sung Sohn, Michael Fadeev, Alessandro Cecconello, Rachel Nechushtai, Itamar Willner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

233 Scopus citations


The synthesis of doxorubicin-loaded metal–organic framework nanoparticles (NMOFs) coated with a stimuli-responsive nucleic acid-based polyacrylamide hydrogel is described. The formation of the hydrogel is stimulated by the crosslinking of two polyacrylamide chains, PA and PB, that are functionalized with two nucleic acid hairpins (4) and (5) using the strand-induced hybridization chain reaction. The resulting duplex-bridged polyacrylamide hydrogel includes the anti-ATP (adenosine triphosphate) aptamer sequence in a caged configuration. The drug encapsulated in the NMOFs is locked by the hydrogel coating. In the presence of ATP that is overexpressed in cancer cells, the hydrogel coating is degraded via the formation of the ATP–aptamer complex, resulting in the release of doxorubicin drug. In addition to the introduction of a general means to synthesize drug-loaded stimuli-responsive nucleic acid-based polyacrylamide hydrogel-coated NMOFs hybrids, the functionalized NMOFs resolve significant limitations associated with the recently reported nucleic acid-gated drug-loaded NMOFs. The study reveals substantially higher loading of the drug in the hydrogel-coated NMOFs as compared to the nucleic acid-gated NMOFs and overcomes the nonspecific leakage of the drug observed with the nucleic-acid-protected NMOFs. The doxorubicin-loaded, ATP-responsive, hydrogel-coated NMOFs reveal selective and effective cytotoxicity toward MDA-MB-231 breast cancer cells, as compared to normal MCF-10A epithelial breast cells.

Original languageAmerican English
Article number1705137
JournalAdvanced Functional Materials
Issue number8
StatePublished - 21 Feb 2018

Bibliographical note

Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim


  • DNA hydrogels
  • adenosine triphosphate (ATP)
  • aptamers
  • metal–organic framework nanoparticles
  • smart material


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