Self-Assembled Cationic β-Cyclodextrin Nanostructures for siRNA Delivery

Singh, Raghvendra Pratap; Hidalgo, Tania; Cazade, Pierre‐André; Darcy, Raphael; Cronin, Michael F.; Dorin, Irina; O’Driscoll, Caitriona M.; Thompson, Damien

doi:10.1021/acs.molpharmaceut.8b01307

Cited by 50 publications

(28 citation statements)

References 64 publications

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“…134 Cyclodextrins have also been proposed to deliver drugs for release in the intestine where bile salts help displace the drug from the complex, as demonstrated in vitro, 137 and have also been developed for siRNA delivery. 143 Supramolecular structures have been used to create artificial enzymes. 148,150 ITC was used to study oxidase-like catalysis using the multiple injection technique developed for studying enzyme kinetics (see above).…”

Section: Supramolecular Structuresmentioning

confidence: 99%

Applications of isothermal titration calorimetry in pure and applied research from 2016 to 2020

Falconer

Schuur

Mittermaier

2021

J of Molecular Recognition

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The last 5 years have seen a series of advances in the application of isothermal titration microcalorimetry (ITC) and interpretation of ITC data. ITC has played an invaluable role in understanding multiprotein complex formation including proteolysistargeting chimeras (PROTACS), and mitochondrial autophagy receptor Nix interaction with LC3 and GABARAP. It has also helped elucidate complex allosteric communication in protein complexes like trp RNA-binding attenuation protein (TRAP) complex.Advances in kinetics analysis have enabled the calculation of kinetic rate constants from pre-existing ITC data sets. Diverse strategies have also been developed to study enzyme kinetics and enzyme-inhibitor interactions. ITC has also been applied to study small molecule solvent and solute interactions involved in extraction, separation, and purification applications including liquid-liquid separation and extractive distillation. Diverse applications of ITC have been developed from the analysis of protein instability at different temperatures, determination of enzyme kinetics in suspensions of living cells to the adsorption of uremic toxins from aqueous streams.

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Section: Supramolecular Structuresmentioning

confidence: 99%

Applications of isothermal titration calorimetry in pure and applied research from 2016 to 2020

Falconer

Schuur

Mittermaier

2021

J of Molecular Recognition

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“…Polycationic cyclodextrins have become the iconic representatives in this category [ 5 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ]. The efficiency in compacting nucleic acids into nanocomplexes (so-called CDplexes) capable of mediating cell entry and subsequent expression of the nucleic acid anticipated activity (transfection) was significantly enhanced for prototypes that can additionally establish cyclodextrin–cyclodextrin interactions through either hydrophobic [ 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ], host–guest [ 79 , 134 ] or aromatic–aromatic contacts [ 135 , 136 , 137 , 138 , 139 , 140 , …”

Section: Biomacromolecule-templated Formation Of Functional Glycocmentioning

confidence: 99%

Cyclodextrin-Based Functional Glyconanomaterials

2020

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Cyclodextrins (CDs) have long occupied a prominent position in most pharmaceutical laboratories as “off-the-shelve” tools to manipulate the pharmacokinetics of a broad range of active principles, due to their unique combination of biocompatibility and inclusion abilities. The development of precision chemical methods for their selective functionalization, in combination with “click” multiconjugation procedures, have further leveraged the nanoscaffold nature of these oligosaccharides, creating a direct link between the glyco and the nano worlds. CDs have greatly contributed to understand and exploit the interactions between multivalent glycodisplays and carbohydrate-binding proteins (lectins) and to improve the drug-loading and functional properties of nanomaterials through host–guest strategies. The whole range of capabilities can be enabled through self-assembly, template-assisted assembly or covalent connection of CD/glycan building blocks. This review discusses the advancements made in this field during the last decade and the amazing variety of functional glyconanomaterials empowered by the versatility of the CD component.

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“…Recently, DNA nanotechnology has rapidly developed to construct a variety of nanocarriers for siRNA delivery based on the good biocompatibility and programmability, such as DNA origami [ 11 ], DNA nanohydrogels [ 12 ], and so on. For these strategies, the integration of siRNAs into DNA nanostructures mainly relies on the hybridization or chemical modification, thus, the unavoidable leakage and degradation, as well as the limited payload capacity may diminish the gene therapy efficiency [ 13 – 15 ]. As an alternative method, in situ generation of siRNAs can significantly enhance the specificity and delivery stability, which thus provides a robust and powerful strategy for cancer therapy [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Endogenous microRNA triggered enzyme-free DNA logic self-assembly for amplified bioimaging and enhanced gene therapy via in situ generation of siRNAs

Jiang

Yue

et al. 2021

J Nanobiotechnol

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Background Small interfering RNA (siRNA) has emerged as a kind of promising therapeutic agents for cancer therapy. However, the off-target effect and degradation are the main challenges for siRNAs delivery. Herein, an enzyme-free DNA amplification strategy initiated by a specific endogenous microRNA has been developed for in situ generation of siRNAs with enhanced gene therapy effect on cervical carcinoma. Methods This strategy contains three DNA hairpins (H1, H2/PS and H3) which can be triggered by microRNA-21 (miR-21) for self-assembly of DNA nanowheels (DNWs). Notably, this system is consistent with the operation of a DNA logic circuitry containing cascaded “AND” gates with feedback mechanism. Accordingly, a versatile biosensing and bioimaging platform is fabricated for sensitive and specific analysis of miR-21 in HeLa cells via fluorescence resonance energy transfer (FRET). Meanwhile, since the vascular endothelial growth factor (VEGF) antisense and sense sequences are encoded in hairpin reactants, the performance of this DNA circuit leads to in situ assembly of VEGF siRNAs in DNWs, which can be specifically recognized and cleaved by Dicer for gene therapy of cervical carcinoma. Results The proposed isothermal amplification approach exhibits high sensitivity for miR-21 with a detection limit of 0.25 pM and indicates excellent specificity to discriminate target miR-21 from the single-base mismatched sequence. Furthermore, this strategy achieves accurate and sensitive imaging analysis of the expression and distribution of miR-21 in different living cells. To note, compared to naked siRNAs alone, in situ siRNA generation shows a significantly enhanced gene silencing and anti-tumor effect due to the high reaction efficiency of DNA circuit and improved delivery stability of siRNAs. Conclusions The endogenous miRNA-activated DNA circuit provides an exciting opportunity to construct a general nanoplatform for precise cancer diagnosis and efficient gene therapy, which has an important significance in clinical translation. Graphic abstract

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Self-Assembled Cationic β-Cyclodextrin Nanostructures for siRNA Delivery

Cited by 50 publications

References 64 publications

Applications of isothermal titration calorimetry in pure and applied research from 2016 to 2020

Applications of isothermal titration calorimetry in pure and applied research from 2016 to 2020

Cyclodextrin-Based Functional Glyconanomaterials

Endogenous microRNA triggered enzyme-free DNA logic self-assembly for amplified bioimaging and enhanced gene therapy via in situ generation of siRNAs

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