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Stimuli-responsive nucleic acid-functionalized metal-organic framework nanoparticles using pH- and metal-ion-dependent DNAzymes as locks.

ABSTRACT: A versatile approach to modify metal-organic framework nanoparticles (NMOFs) with nucleic acid tethers, using the "click chemistry" method is introduced. The nucleic acid-functionalized NMOFs are used to prepare stimuli-responsive carriers of loads (fluorescence probes or anti-cancer drugs). Two different stimuli-responsive nucleic acid-based NMOFs are presented. One system involves the preparation of pH-responsive NMOFs. The NMOFs are loaded with fluorophores or doxorubicin anti-cancer drug and locked in the NMOFs by pH-responsive DNA duplex capping units. At pH = 5.0 the capping units are unlocked, leading to the release of the loads. The AS1411 aptamer is conjugated to the locking units as the targeting unit for the nucleolin biomarker present in cancer cells. The pH-responsive doxorubicin-loaded NMOFs and, in particular, the AS1411 aptamer-modified pH-responsive NMOFs reveal selective, targeted, cytotoxicity toward MDA-MB-231 breast cancer cells. A second system involves the synthesis of NMOFs that are loaded with fluorophores or doxorubicin and capped with metal-ion-dependent DNAzyme/substrate complexes as locking units (metal ion = Mg2+ or Pb2+ ions). In the presence of the respective metal ions, the nucleic acid locking units are cleaved off, resulting in the release of the loads. Also, "smart" Mg2+-ion-dependent DNAzyme capped doxorubicin-loaded NMOFs are synthesized via the integration of the ATP aptamer sequence in the loop domain of the Mg2+-dependent DNAzyme. The unlocking of these NMOFs proceeds effectively only in the presence of ATP and Mg2+ ions, acting as cooperative triggers. As ATP is over-expressed in cancer cells, the "smart" carrier provides sense-and-treat functions. The "smart" ATP/Mg2+-triggered doxorubicin-loaded NMOFs reveal selective cytotoxicity toward MDA-MB-231 cancer cells. Beyond the use of the metal-ion-dependent DNAzymes as ion-responsive locks of drug-loaded NMOF carriers, the DNAzyme-capped fluorophore-loaded NMOFs are successfully applied as functional units for multiplexed ion-sensing and for the design of logic-gate systems.

SUBMITTER: Chen WH

PROVIDER: S-EPMC5621505 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Stimuli-responsive nucleic acid-functionalized metal-organic framework nanoparticles using pH- and metal-ion-dependent DNAzymes as locks.

Chen Wei-Hai WH Yu Xu X Cecconello Alessandro A Sohn Yang Sung YS Nechushtai Rachel R Willner Itamar I

Chemical science 20170606 8

A versatile approach to modify metal-organic framework nanoparticles (NMOFs) with nucleic acid tethers, using the "click chemistry" method is introduced. The nucleic acid-functionalized NMOFs are used to prepare stimuli-responsive carriers of loads (fluorescence probes or anti-cancer drugs). Two different stimuli-responsive nucleic acid-based NMOFs are presented. One system involves the preparation of pH-responsive NMOFs. The NMOFs are loaded with fluorophores or doxorubicin anti-cancer drug and ...[more]

PMID: 28989617

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Project description:Mercaptoundecanoic acid (MUA) functionalized gold nanoparticles (AuNP-MUA) were synthesized and demonstrated to possess pH-triggered aggregation and re-dispersion, as well as the capability of phase transfer between aqueous and organic phases in response to changes in pH. The pH of aggregation for AuNP-MUA is consistent with the pKa of MUA (pH ~4) in solution, while AuNP-MUA phase transition between aqueous and organic phases occurs at pH ~9. The ion pair formation between the amine group in octadecylamine (ODA), the carboxylate group in MUA, and the hydrophobic alkyl chain of ODA facilitates the phase transfer of AuNP-MUA into an organic medium. The AuNP-MUA were investigated as a reusable catalyst in the catalytic reduction of 4-nitrophenol by borohydride-a model reaction for AuNPs. It was determined that 100% MUA surface coverage completely inhibits the catalytic activity of AuNPs. Decreasing the surface coverage was shown to increase catalytic activity, but this decrease also leads to decreased colloidal stability, recoverability, and reusability in subsequent reactions. At 60% MUA surface coverage, colloidal stability and catalytic activity were achieved, but the surface coverage was insufficient to enable redispersion following pH-induced recovery. A balance between AuNP colloidal stability, recoverability, and catalytic activity with reusability was achieved at 90% MUA surface coverage. The AuNP-MUA catalyst can also be recovered at different pH ranges depending on the recovery method employed. At pH ~4, protonation of the MUA results in reduced surface charge and aggregation. At pH ~9, ODA will form an ion-pair with the MUA and induce phase transfer into an immiscible organic phase. Both the pH-triggered aggregation/re-dispersion and aqueous/organic phase transfer methods were employed for catalyst recovery and reuse in subsequent reactions. The ability to recover and reuse the AuNP-MUA catalyst by two different methods and different pH regimes is significant, based on the fact that nanoparticle-catalyzed reactions may occur under different pH conditions.

Dataset Information

Stimuli-responsive nucleic acid-functionalized metal-organic framework nanoparticles using pH- and metal-ion-dependent DNAzymes as locks.

Publications

Stimuli-responsive nucleic acid-functionalized metal-organic framework nanoparticles using pH- and metal-ion-dependent DNAzymes as locks.

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