Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles: delivery and bioactivity in pancreatic cancer cells

Cogoi, Susanna; Jakobsen, Ulla; Pedersen, Erik B.; Vogel, Stefan; Xodo, Luigi E.

doi:10.1038/srep38468

Cited by 29 publications

(27 citation statements)

References 39 publications

(85 reference statements)

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“…Chemical modifications, on the other hand, employed hydrophobic interactions or covalent ligations to introduce chemical ligands or functional molecules onto exosomal surfaces. 21–23 However, hydrophobic probes are randomly inserted on exosome surfaces, and thus lack of precision and specificity. And that covalent ligations usually requires harsh conditions for chemical reactions, which could possibly affect the structure and function of exosomes and give rise to safety concerns.…”

mentioning

confidence: 99%

Molecular Recognition-Based DNA Nanoassemblies on the Surfaces of Nanosized Exosomes

et al. 2017

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Exosomes are membrane-enclosed extracellular vesicles derived from cells, carrying biomolecules that include proteins and nucleic acids for intercellular communication. Owning to their advantages of size, structure, stability, and biocompatibility, exosomes have been used widely as natural nanocarriers for intracellular delivery of theranostic agents. Meanwhile, surface modifications needed to endow exosomes with additional functionalities remain challenging by their small size and the complexity of their membrane surfaces. Current methods have used genetic engineering and chemical conjugation, but these strategies require complex manipulations and have only limited applications. Herein, we present an aptamer-based DNA nanoassemblies on exosome surfaces. This in situ assembly method is based on molecular recognition between DNA aptamers and their exosome surface markers, as well as DNA hybridization chain reaction initiated by an aptamer-chimeric trigger. It further demonstrated selective assembly on target cell-derived exosomes, but not exosomes derived from nontarget cells. The present work shows that DNA nanostructures can successfully be assembled on a nanosized organelle. This approach is useful for exosome modification and functionalization, which is expected to have broad biomedical and bioanalytical applications.

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confidence: 99%

Molecular Recognition-Based DNA Nanoassemblies on the Surfaces of Nanosized Exosomes

et al. 2017

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“…In contrast, replacement of both TT loops with H 15 resulted in ΔT m = +0.6°C, which might refer to stacking interactions of H 15 moieties over the underlying G-quartet according to molecular modeling studies. [5,57,58] Molecular modeling suggests that such significant increases could be a result of stacking interactions between two anthraquinone monomers.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and Molecular Modeling of Thermally Stable DNA G‐Quadruplexes with Anthraquinone Insertions

2017

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Two new phosphoramidite building blocks for DNA synthesis were synthesized from 1,5‐ and 2,6‐dihydroxyanthraquinones through alkylation with 3‐bromo‐1‐propanol followed by DMT‐protection. The novel synthesized 1,5‐ and 2,6‐disubstituted anthraquinone monomers H15 and H26 are incorporated into a G‐quadruplex by single and double replacements of TGT and TT loops. Monomers H15 and H26 were found to destabilize G‐quadruplex structures for all single replacements of TGT or TT loops. The largest destabilization was observed when H26 linker replaced a TT loop. In contrast, the presence of anthraquinone monomers in two TT loops led to 1–18 °C increase in their thermal stabilities, depending on linker attachment geometry of the monomers. The presence of H15 and H26 linkers replacing two TT loops results in the highest stabilization of the G‐quadruplex structure by 18.2 °C. Circular dichroism spectroscopy of all anthraquinone‐modified quadruplexes revealed no change of the antiparallel structure when compared with the wild type under potassium buffer conditions. The significantly increased thermostabilities were interpreted by molecular modeling of anthraquinone‐modified G‐quadruplexes.

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“…xenograft mice [113]. Moreover, the authors subsequently reported a lipid-modified strategy based on the use of palmitoyl-oleyl-phosphatidylcholine liposomes, which improved the delivery of the G4-decoy by coupling to the liposomes efficiently, resulting in decreased Kras transcription levels and metabolic activity of pancreatic cancer cells [114].…”

Section: Decoysmentioning

confidence: 99%

Clinical Potential of Oligonucleotide Therapeutics against Pancreatic Cancer

Takakura¹,

Kawamura²,

Torisu³

et al. 2019

Preprint

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Although there is a several array of diagnostic and therapeutic choices for pancreatic cancer in recent years, a crucial medical approach for the refractory disease is still needed. Oligonucleotide therapeutics, such as those based on antisense RNAs, RNA interference, aptamers and decoys, are promising agents against pancreatic cancer because they identify a specific nucleotide sequence or protein and interfere with gene expression as molecular-targeted agents. Within just the past quarter-century, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Actually, there have been several clinical and preclinical studies of oligonucleotides for patients with pancreatic cancer so far. To support the discovery of effective diagnostic or therapeutic options by using oligonucleotide-based strategies in the absence of satisfactory therapies for long-term survival and the rising trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients with underlying preclinical or scientific data and focus on the possibility of oligonucleotides to target pancreatic cancer in clinical implications.

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Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles: delivery and bioactivity in pancreatic cancer cells

Cited by 29 publications

References 39 publications

Molecular Recognition-Based DNA Nanoassemblies on the Surfaces of Nanosized Exosomes

Molecular Recognition-Based DNA Nanoassemblies on the Surfaces of Nanosized Exosomes

Synthesis and Molecular Modeling of Thermally Stable DNA G‐Quadruplexes with Anthraquinone Insertions

Clinical Potential of Oligonucleotide Therapeutics against Pancreatic Cancer

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