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

Nanoscale
Wei-Hai ChenItamar Willner

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-l...Continue Reading

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Methods Mentioned

BETA
Fluorescence
confocal microscopy

Software Mentioned

IncuCyte Zoom System

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