Selective enhancement of nucleases by polyvalent DNA-functionalized gold nanoparticles (original) (raw)

Gold Nanoparticles for Vectorization of Nucleic Acids for Cancer Therapeutics

Molecules, 2020

Cancer remains a complex medical challenge and one of the leading causes of death worldwide. Nanomedicines have been proposed as innovative platforms to tackle these complex diseases, where the combination of several treatment strategies might enhance therapy success. Among these nanomedicines, nanoparticle mediated delivery of nucleic acids has been put forward as key instrument to modulate gene expression, be it targeted gene silencing, interference RNA mechanisms and/or gene edition. These novel delivery systems have strongly relied on nanoparticles and, in particular, gold nanoparticles (AuNPs) have paved the way for efficient delivery systems due to the possibility to fine-tune their size, shape and surface properties, coupled to the ease of functionalization with different biomolecules. Herein, we shall address the different molecular tools for modulation of expression of oncogenes and tumor suppressor genes and discuss the state-of-the-art of AuNP functionalization for nuclei...

Stability of Gold Nanoparticle-Bound DNA toward Biological, Physical, and Chemical Agents

Chemical Biology <html_ent glyph="@amp;" ascii="&"/> Drug Design, 2006

Positively charged trimethylammonium-modified mixed monolayer protected clusters (MMPCs) interact with DNA by complementary electrostatic binding, serving as efficient DNA delivery systems. The stability of gold nanoparticle-bound DNA toward biological, physical, and chemical agents is investigated. The MMPC-bound DNA is efficiently protected from DNAse I digestion and experiences nicking/cleavage-induced morphology changes with higher concentrations of DNAse I. Significant protection of MMPC-bound DNA was also observed in a physical sonication assay. However, the MMPC-bound DNA was found to show enhanced cleavage upon exposure to chemically induced radicals. The latter may indicate that bound DNA is bent and wrapped on the surface of the cationic MMPC.

Gold-Aryl nanoparticles coated with polyelectrolytes for adsorption and protection of DNA against nuclease degradation

Applied Organometallic Chemistry, 2019

Binding DNA on nanoparticles was pursued to form nanoplatform for formation of non-viral gene system. Carboxyl derivatized gold-aryl nanoparticles can bind with biodegradable cationic polyelectrolytes such as polydiallyldimethylammonium chloride (PDADMAC). In our study, we used gold-aryl nanoparticles (AuNPs) treated with PDADMAC to form conjugates with non-thiol or non-disulfide modified oligonucleotide DNA. Both AuNPs-DNA and PDADMAC-AuNPs-DNA biomaterials were characterized using UV-Vis, dynamic light scattering (DLS), atomic force microscopy (AFM), transmission electron microscopy (TEM) and agarose gel electrophoresis. UV-Vis showed a red shift in the plasmon peak as compared with unconjugated AuNPs. DLS measurements also showed difference in the size of AuNPs-DNA and PDADMAC-AuNPs-DNA. AFM and TEM results showed proper conjugation of DNA with AuNPs. Gel electrophoresis proved the presence of interaction between PDADMAC-AuNPs and negatively charged DNA. The binding of DNA in the described bioconjugate enhanced its protection against nuclease degradation and prolonged its presence in the digestive environment of DNase-I. From the results we expect that these biomaterials can be used in nanomedicine with emphasis on non-viral gene system.

Binding of single stranded nucleic acids to cationic ligand functionalized gold nanoparticles

Biointerphases, 2016

The interactions of nanoparticles (NPs) with single stranded nucleic acids (NAs) have important implications in gene delivery, and nanotechnological and biomedical applications. Here, the complexation of cationic ligand functionalized gold nanoparticles with single stranded deoxyribose nucleic acid (DNA) and ribonucleic acid (RNA) are examined using all atom molecular dynamics simulations. The results indicated that complexation depends mostly on charge of nanoparticle, and, to lesser extent, sequence and type of nucleic acid. For cationic nanoparticles, electrostatic interactions between charged ligands and the nucleic acid backbone dominate binding regardless of nanoparticle charge. Highly charged nanoparticles bind more tightly and cause compaction of the single-stranded NAs through disruption of intrastrand π-π stacking and hydrogen bonding. However, poly-purine strands (polyA-DNA, polyA-RNA) show less change in structure than poly-pyrimidine strands (polyT-DNA, polyU-RNA). Over...

Locked Nucleic Acid-Modified Antisense miR-10b Oligonucleotides Form Stable Duplexes on Gold Nanoparticles

The interaction of locked nucleic acid (LNA)-modified antisense miR-10b oligonucleotides and its complementary DNA (cDNA) analog is studied using gold nanoparticles. We demonstrate that LNA shows a slower hybridization rate with complementary DNA molecules, however improves the melting temperature (∼15 °C) and duplex stability significantly. The dramatic difference in melting temperatures between the LNA–cDNA and DNA–cDNA duplexes is examined through the change in aggregation of gold nanoparticles by monitoring the absorbance values at 525, 570, and 600 nm. Furthermore, the difference in melting temperatures enables us to control gold nanoparticle assembly/disassembly with free DNA/LNA oligonucleotides at various temperatures. This heat-induced rearrangement of gold nanoparticles and oligonucleotides is monitored by naked eye and UV–Vis spectroscopy. Owing to the remarkable duplex stability with complementary oligonucleotides, LNA not only plays an important role in medicine but also is a significant tool in biomaterials science.

Inhibition of DNA Transcription Using Cationic Mixed Monolayer Protected Gold Clusters

Journal of the American Chemical Society, 2001

Efficient recognition of DNA is a prerequisite for the development of biological effectors, including transcription and translation regulators, transfection vectors, and DNA sensors. To provide an effective scaffold for multivalent interactions with DNA, we have fabricated mixed monolayer protected gold clusters (MMPCs) functionalized with tetraalkylammonium ligands that can interact with the DNA backbone via charge complementarity. Binding studies indicate that the MMPCs and DNA form a charge-neutralized, nonaggregated assembly. The interactions controlling these assemblies are highly efficient, completely inhibiting transcription by T7 RNA polymerase in vitro.

Gold nanoparticle design for RNA compaction

Biointerphases

RNA-based therapeutics hold a great promise in treating a variety of diseases. However, double-stranded RNAs (dsRNAs) are inherently unstable, highly charged, and stiff macromolecules that require a delivery vehicle. Cationic ligand functionalized gold nanoparticles (AuNPs) are able to compact nucleic acids and assist in RNA delivery. Here, we use large-scale all-atom molecular dynamics simulations to show that correlations between ligand length, metal core size, and ligand excess free volume control the ability of nanoparticles to bend dsRNA far below its persistence length. The analysis of ammonium binding sites showed that longer ligands that bind deep within the major groove did not cause bending. By limiting ligand length and, thus, excess free volume, we have designed nanoparticles with controlled internal binding to RNA's major groove. NPs that are able to induce RNA bending cause a periodic variation in RNA's major groove width. Density functional theory studies on s...

DNA-binding by Functionalized Gold Nanoparticles: Mechanism and Structural Requirements

Chemical Biology <html_ent glyph="@amp;" ascii="&"/> Drug Design, 2006

A family of nanoparticles featuring surfaces of varying hydrophobicity was synthesized. The efficiency of DNA-binding was determined, demonstrating in a fivefold modulation in binding a 37-mer DNA strand. Nanoparticle-binding causes a reversible conformational change in the DNA structure, as demonstrated by circular dichroism and fluorescence experiments. Furthermore, the affinity of the nanoparticle for the DNA can be regulated by external agents, though stability of the complex is observed at relatively high ionic strengths.