High-performance method for specific effect on nucleic acids in cells using TiO2~DNA nanocomposites

Левина, А. С.; Репкова, М. Н.; Ismagilov, Z. R.; Shikina, N. V.; Malygin, E. G.; Мазуркова, Н. А.; Zinov'ev, V V; Evdokimov, Alexey A.; Байбородин, С. И.; Зарытова, В. Ф.

doi:10.1038/srep00756

Cited by 36 publications

(22 citation statements)

References 41 publications

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“…They prepared a DNA/polylysine conjugate, where the positively charged polylysine is used to anchor on titania surface and the DNA fragment can hybridize to its complementary strand. 18,19 To make the attachment chemistry more cost-effective, it is desirable to directly adsorb nonmodified DNA. Zhu et al studied the adsorption of calf thymus DNA by TiO2 NPs and they concluded that phosphate is responsible for DNA adsorption based on IR spectroscopy.…”

Section: Introductionmentioning

confidence: 99%

Adsorption of DNA Oligonucleotides by Titanium Dioxide Nanoparticles

et al. 2014

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Titanium dioxide (TiO2) or titania shows great promise in detoxification and drug delivery. To reach its full potential, it is important to interface TiO2 with biomolecules to harness their molecular recognition function. To this end, DNA attachment is an important topic. Previous work has mainly focused on long double-stranded DNA or single nucleotides. For biosensor development and targeted drug delivery, it is more important to use single-stranded oligonucleotides. Herein, the interaction between fluorescently labeled oligonucleotides and TiO2 nanoparticles is reported. The point of zero charge (PZC) of TiO2 is around 6 in water or in acetate buffer, so they are positively charged at lower pH.However, if in phosphate or citrate buffer, the particles are negatively charged even at pH ~2, suggesting strong adsorption of buffer anions. DNA adsorption takes places mainly via the phosphate backbone although the bases might also have moderate contributions. Peptide nucleic acids (PNA) with an amide backbone cannot be adsorbed. DNA adsorption is strongly affected by inorganic anions, where phosphate and citrate can strongly inhibit DNA adsorption. DNA adsorption is also promoted by adding salt or lowering pH. DNA adsorption is accompanied with fluorescence quenching and doublestranded DNA showed reduced quenching, allowing detection of DNA using TiO2 nanoparticles.3

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Section: Introductionmentioning

confidence: 99%

Adsorption of DNA Oligonucleotides by Titanium Dioxide Nanoparticles

et al. 2014

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“…The antiviral activity of the Si–NH 2 ·ODN(4) nanocomplex was not inferior to that of the TiO 2 ·PL–ODN nanocomplexes reported in our previous papers [20–22]. The high inhibition efficiency of the virus reproduction with the use of the Si–NH 2 ·ODN nanocomplex is provided by the fact that the nanocomplex delivers ODN into the cytoplasm of the cell, and ODN can penetrate into the cell nuclei (Fig.…”

Section: Resultsmentioning

confidence: 63%

“…The experiments were carried out similarly as described in [20]. In short: Two days after the formation of a continuous monolayer of MDCK cells at 37 °C and 5% CO 2 , the cells were washed with nutrient medium without serum.…”

Section: Methodsmentioning

confidence: 99%

Non-agglomerated silicon–organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties

Левина¹,

Репкова²,

Shikina³

et al. 2018

Beilstein J. Nanotechnol.

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The development of efficient and convenient systems for the delivery of nucleic-acid-based drugs into cells is an urgent task. А promising approach is the use of various nanoparticles. Silica nanoparticles can be used as vehicles to deliver nucleic acid fragments into cells. In this work, we developed a method for the synthesis of silicon–organic (Si–NH2) non-agglomerated nanoparticles by the hydrolysis of aminopropyltriethoxysilane (APTES). The resulting product forms a clear solution containing nanoparticles in the form of low molecular weight polymer chains with [─Si(OH)(C3H6NH2)O─] monomer units. Oligonucleotides (ODN) were conjugated to the prepared Si–NH2 nanoparticles using the electrostatic interaction between positively charged amino groups of nanoparticles and negatively charged internucleotide phosphate groups in oligonucleotides. The Si–NH2 nanoparticles and Si–NH2·ODN nanocomplexes were characterized by transmission electron microscopy, atomic force microscopy and IR and electron spectroscopy. The size and zeta potential values of the prepared nanoparticles and nanocomplexes were evaluated. Oligonucleotides in Si–NH2·ODN complexes retain their ability to form complementary duplexes. The Si–NH2 Flu nanoparticles and Si–NH2·ODNFlu nanocomplexes were shown by fluorescence microscopy to penetrate into human cells. The Si–NH2 Flu nanoparticles predominantly accumulated in the cytoplasm whereas ODNFlu complexes were predominantly detected in the cellular nuclei. The Si–NH2·ODN nanocomplexes demonstrated a high antisense activity against the influenza A virus in a cell culture at a concentration that was lower than their 50% toxic concentration by three orders of magnitude.

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“…Many researches choose the same segment to study antiviral activity of nucleic acid-based drugs [e.g., 12]. At first, it was shown that TiO 2 •PL-DNA and TiO 2 •PL±DNA nanocomposites showed a low toxicity (TC 50 1500 g/ml) in the MDCK cell culture [13,14]. To inhibit the reproduction of IAV, we used the nontoxic concentration of the nanocomposites (5 g/ml) corresponding to 0.1 μM for oligonucleotides (20 nmol/mg).…”

Section: Resultsmentioning

confidence: 99%

TiO2∼DNA nanocomposites as efficient site-specific antiviral agents against influenza A virus in cell culture

Левина

Репкова

Зарытова

et al. 2015

2015 IEEE 15th International Conference on Nanotechnology (IEEE-NANO)

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The development of new antiviral nucleic acidbased drugs and the search for their efficient delivery into cells are an urgent task. We developed methods of immobilizing DNA fragments to titanium dioxide nanoparticles with the formation of TiO 2~D NA nanocomposites. It is shown that DNA fragments in nanocomposites retain their ability to form complementary complexes and can be delivered into cells without transfection agents and other methods of exposure. The proposed nanocomposites were shown to be efficient agents to affect target nucleic acids inside cells with an example of inhibition of influenza A virus (IAV) reproduction. The nanocomposites bearing the DNA 1 fragment targeted to the 3'-noncoding region of segment 5 (-)vRNA showed a low toxicity (TC 50 1500 g/ml) and a high antiviral activity against different IAV subtypes (H1N1, H5N1, and H3N2) in infected MDCK cells (the virus replication was inhibited by up to four orders of magnitude). The IC 50 value for nanocomposites was estimated to be 1.5 g/ml (30 nM for DNA), so its selectivity index was calculated as ~1000. Control samples, i.e., nanoparticles without DNA fragments and vise versa as well as unbound DNA fragments in the presence of nanoparticles were much less active, if at all. A high sitespecificity of the action of designed nanocomposites (~3000-fold difference between the effect of the nanocomposites containing target-directed DNA and DNA with a random sequence) indicates a pronounced antisense effect. The presented types of nanocomposites can be applied in the thriving technology of drug delivery to achieve high therapeutic and biological efficacy.

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High-performance method for specific effect on nucleic acids in cells using TiO2~DNA nanocomposites

Cited by 36 publications

References 41 publications

Adsorption of DNA Oligonucleotides by Titanium Dioxide Nanoparticles

Adsorption of DNA Oligonucleotides by Titanium Dioxide Nanoparticles

Non-agglomerated silicon–organic nanoparticles and their nanocomplexes with oligonucleotides: synthesis and properties

TiO2∼DNA nanocomposites as efficient site-specific antiviral agents against influenza A virus in cell culture

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