Targeted VEGF-triggered release of an anti-cancer drug from aptamer-functionalized metal-organic framework nanoparticles

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Amino-triphenyl dicarboxylate-bridged Zr4+ metal-organic framework nanoparticles (NMOFs), 100-130 nm, are modified with a nucleic acid complementary to the VEGF aptamer. The nucleic acid-functionalized NMOFs were loaded with the anti-cancer drug doxorubicin (or Rhodamine 6G as a drug model), and the loaded NMOFs were capped by hybridization with the VEGF aptamer that yielded VEGF-responsive duplex nucleic acid gates. In the presence of VEGF, a biomarker over-expressed in cancer cells, selective unlocking of the gates proceeds through the formation of VEGF/aptamer complexes, resulting in the release of the loads. In addition, the VEGF aptamer locking units were conjugated to the AS1411 aptamer sequence that binds to nucleolin receptors associated with cancer cells, resulting in the construction of cancer-cell targeted VEGF-responsive doxorubicin-loaded NMOFs. The different drug-loaded stimuli-responsive NMOFs reveal selective permeation into MDA-MB-231 breast cancer cells, compared to their incorporation into normal MCF-10A breast cells, with a two-fold enhanced incorporation into the MDA-MB-231 cells of the AS1411 aptamer-functionalized NMOFs. Cytotoxicity experiments revealed impressive selective apoptosis of the doxorubicin-loaded NMOFs towards the MDA-MB-231 cancer cells compared to the normal MCF-10A breast cells. A 55% and 70% MDA-MB-231 cell apoptosis was observed upon subjecting the cells to the VEGF aptamer and the VEGF aptamer/AS1411 aptamer conjugate-caged NMOFs, respectively, for a time-interval of three days, where only <10% apoptosis of the MCF-10A cells was observed under similar conditions.

Original languageAmerican English
Pages (from-to)4650-4657
Number of pages8
JournalNanoscale
Volume10
Issue number10
DOIs
StatePublished - 14 Mar 2018

Bibliographical note

Publisher Copyright:
© 2018 The Royal Society of Chemistry.

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