MicroRNA-Guided Selective Release of Loads from Micro-/Nanocarriers Using Auxiliary Constitutional Dynamic Networks

Pu Zhang, Liang Yue, Margarita Vázquez-González, Zhixin Zhou, Wei Hai Chen, Yang Sung Sohn, Rachel Nechushtai, Itamar Willner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Two different drug micro-carriers consisting of doxorubicin-dextran (DOX-D)- and camptothecin-modified carboxymethyl cellulose (CPT-CMC)-loaded nucleic acid-stabilized microcapsules, MC-1 and MC-2, or two different nanocarriers consisting of nucleic-acid-locked doxorubicin (DOX)- and camptothecin (CPT)-loaded metal-organic framework nanoparticles, NMOF-1 and NMOF-2, are coupled to auxiliary constitutional dynamic networks, CDNs, for the triggered release of the drugs. CDN "S" composed of four constituents AA′', AB′, BA′, and BB′, and two hairpin structures, H1 and H2, leads to the CDN "S"-guided unlocking of the MC-1/MC-2 carriers and the release of DOX-D and CPT-CMC or of the NMOF-1 and NMOF-2 carriers that release DOX and CPT, respectively. The unlocking processes are activated by the cleavage of H1 and H2 by BB′ and BA′, respectively, to yield fragmented strands that unlock the gating units of the microcapsules/NMOFs carriers. In the presence of miRNA-155 or miRNA-124, dictated orthogonal reconfiguration of CDN "S" into CDN "X" or "Y" proceeds. The miRNA-155 stimulates the reconfiguration of CDN "S" to CDN "X", where AA′ and BB′ are upregulated, and AB′ and BA′ are downregulated, leading to the enhanced release of DOX-D or DOX from the microcapsule/NMOFs carriers, and to the concomitant inhibition of the release of CPT-CMC or CPT from the respective carriers. Similarly, the miRNA-124-triggered reconfiguration of CDN "S" to CDN "Y" results in the BA′-guided cleavage of H2 and the preferred release of CPT-CMC or CPT from the respective carriers. The miRNA-triggered CDN-driven unlocking of the carriers stimulates the amplified and selective release of the drugs from the microcapsules/NMOFs carriers.

Original languageAmerican English
Pages (from-to)1482-1491
Number of pages10
JournalACS Nano
Volume14
Issue number2
DOIs
StatePublished - 25 Feb 2020

Bibliographical note

Publisher Copyright:
Copyright © 2020 American Chemical Society.

Keywords

  • metal-organic framework
  • miRNA-124
  • miRNA-155
  • microcapsule
  • nanomedicine
  • nanoparticle

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