Smart Mesoporous SiO₂ Nanoparticles for the DNAzyme-Induced Multiplexed Release of Substrates

The fluorescent dyes methylene blue, MB⁺, and thionine, Th⁺, can be trapped in the pores of mesoporous silica, MP-SiO₂, by means of functional nanostructures consisting of the Mg²⁺- or Zn²⁺-dependent DNAzyme sequences. In the presence of Mg²⁺ or Zn²⁺ ions the respective DNAzymes are activated, leading to the specific cleavage of the respective caps, and the selective release of MB⁺ or Th⁺. The enlargement of the conserved loop domains of the Mg²⁺- or Zn²⁺-dependent DNAzyme sequences with foreign nucleotides prohibits the formation of active DNAzymes and eliminates the release of the respective dyes. This is due to the flexibility of the loops that lacks affinity for the association of the ions. The insertion of aptamer sequences (e.g., the adenosine-5′-triphosphate (ATP) aptamer) or ion-binding sequences (e.g., T-rich Hg²⁺ ion-binding domains) as foreign components to the loop regions allows the formation of active Mg²⁺- or Zn²⁺-dependent DNAzyme structures through the cooperative formation of aptamer-ATP complexes or T-Hg²⁺-T bridges. These aptamer–substrate complexes or T-Hg²⁺-T bridges allosterically stabilize and activate the DNAzymes, thus allowing the selective release of the fluorescent substrates MB⁺ or Th⁺. The metal ion-driven DNAzyme release of substrates from the pores of MP-SiO₂, and particularly the allosteric activation of the DNAzymes through cooperative aptamer–substrate complexes or metal-ion bridges, has important future nanomedical implications for targeted release of drugs. This is demonstrated with the triggered release of the anticancer drug, doxorubicin, by the Mg²⁺-DNAzyme-locked pores or by the aptamer-ATP complex-triggered activation of the Mg²⁺-dependent DNAzyme

Light-Induced Aggregation of Gold Nanoparticles and Photoswitching of Silicon Surface Potential

Hybrid nanomaterials having tunable properties that can be reversibly conducted by external stimuli, in a particular light, are of great importance since they enable synergetic behavior between their components and enable the design of stimuli responsive “smart” materials and surfaces. Here we describe the formation of organic–inorganic hybrid nanoparticles that photochemically aggregate and their effect on the electronic properties of a semiconducting surface, as a function of external irradiation. The inorganic component consists of 3 nm gold nanoparticles while the organic component is a covalently attached, photochromic spiropyran derivative. Aggregation/deaggregation patterns in solution were obtained and analyzed by UV–vis spectroscopy and transmission electron microscopy upon photoswitching. The assembly of spiropyran-modified gold nanoparticles on an Si/SiO₂ surface proved useful in phototuning the electronic properties of semiconductors measured by contact potential difference

Biocatalytic Release of an Anticancer Drug from Nucleic-Acids-Capped Mesoporous SiO₂ Using DNA or Molecular Biomarkers as Triggering Stimuli

DNA-gated mesoporous SiO₂ nanoparticles, MP-SiO₂ NPs, loaded with rhodamine B, RhB, act as “smart” materials that reveal complementary “sense” and “release” functionalities. The unlocking of the DNA pore-capping units is achieved by the biocatalytic cleavage of the DNA, and the unlocking process is amplified by the regeneration of the analyte-trigger. The RhB-loaded MP-SiO₂ NPs are capped with nucleic acid hairpin structures that lock the RhB in the pores. Opening of the hairpin structures by a nucleic acid analyte trigger or by the formation of an aptamer–substrate (ATP) complex leads to the formation of duplex structures being cleaved by exonuclease III, Exo III, or the nicking enzyme, Nb. BbvCI. This results in the regeneration of the target analytes, the autonomous unlocking of the pores, and the release of RhB. The systems reveal selectivity, and one-, two-, three-base mutations in the target DNA, or substitution of ATP with other triphosphate nucleotides, prohibit the unlocking of the pores. In analogy to the biocatalytic release of the model fluorophore substrates, the anticancer drug camptothecin, CPT, was entrapped in the pores and locked by the <b>1</b> or <b>11</b> hairpin structures. The drug was released from the pores in the presence of the nucleic acid <b>2</b> or ATP and the Exo III, as biocatalyst. Similarly, CPT locked in the pores by the <b>6</b> or <b>12</b> hairpins were released from the pores in the presence of ATP and Nb. BbvCI, as nicking enzyme, respectively. The effects of the CPT-loaded MP-SiO₂ NPs, capped with the ATP-dependent lock <b>6</b>, on the viability of MDA-231 breast cancer cells and MCF-10a normal breast cells were examined. We find that after 48 h, 65% cell death was observed for the MDA-231 cancer cells, where only 25% cell death was observed for the normal cells. The higher cell death of the cancer cells correlates well with the enhanced metabolic synthesis of ATP in the cancerous cells