• Filter By:
• Specialty
• Source
• Condition
• Cancer
• Infectious Disease
• Drug
• Training
• Management
• Procedure
• Therapy
• Vaccine
• Nutrition
• Country

Mitochondria-Targeted Gene Silencing Facilitated by Mito-CPDs
We report herein a universal mitochondria-targeted gene-delivery approach by using cell-penetrating poly(disulfide)s (CPDs). Novel CPD-based mitochondrial transporters, named Mito-CPDs, were synthesized by using triphenylphosphonium (TPP)-fused propagating monomers containing either disulfide or diselenide backbones. Upon spontaneous complex formation with an oligonucleotide (single- or double-stranded), the resulting nanoscale Mito-CPD@Oligo exhibited excellent properties in common biological media. While the intracellular gene-delivery efficiency of these Mito-CPDs was comparable to that of commercial transfection agents...
Source: Chemistry - February 22, 2023 Category: Chemistry Authors: Wenjie Lang Wei Tan Bizhong Zhou Yuli Zhuang Bei Zhang Linye Jiang Shao Q Yao Jingyan Ge Source Type: research

A triazolium-anchored self-immolative linker enables self-assembly-driven siRNA binding and esterase-induced release
Chemistry. 2022 Nov 8. doi: 10.1002/chem.202203311. Online ahead of print.ABSTRACTThe increased importance of RNA-based therapeutics comes with a need to develop next-generation stimuli-responsive systems capable of binding, transporting and releasing RNA oligomers. In this work, we describe triazolium-based amphiphiles capable of siRNA binding and enzyme-responsive release of the nucleic acid payload. In aqueous medium, the amphiphile selfassembles into nanocarriers that can disintegrate upon the addition of esterase. Key to the molecular design is a self-immolative linker that is anchored to the triazolium moiety and act...
Source: Chemistry - November 8, 2022 Category: Chemistry Authors: Selina Hollstein Lamiaa M A Ali Maeva Coste Julian Vogel Nadir Bettache S ébastien Ulrich Max von Delius Source Type: research

Structure-Activity Relationships in Nucleic-Acid-Templated Vectors Based on Peptidic Dynamic Covalent Polymers
We describe the combinations that lead to nucleic acid complexation, in saline buffer, using different templates, from short siRNA to long DNA. Finally, we identify a successful peptidic DCP featuring six-arginine repeating unit that promote the safe and effective delivery of siRNA in live cancer cells.PMID:36342312 | DOI:10.1002/chem.202202921
Source: Chemistry - November 7, 2022 Category: Chemistry Authors: Dan-Dan Su Lamiaa M A Ali Ma ëva Coste Nabila Laroui Yannick Bessin Mihail Barboiu Nadir Bettache Sebastien Ulrich Source Type: research

Glutathione-Responsive Heterogeneous Metal-Organic Framework Hybrids for Photodynamic-Gene Synergetic Cell Apoptosis
Chemistry. 2022 Mar 20. doi: 10.1002/chem.202200305. Online ahead of print.ABSTRACTIntracellular excessive glutathione (GSH) consumes the cytotoxic 1 O 2 significantly, restricting the development and efficacy of 1 O 2 -mediated photodynamic therapy (PDT). To face with this challenge, herein a heterogeneous metal-organic framework (MOF) nanohybrid was sequentially fabricated with porous coordination network-typed MOF as the core and photosensitizer, and Cu II -centered zeolitic imidazolate framework-67 as shell encapsulating cyanine 3-labelled siRNA. Upon internalized by cells and activated by GSH, the outer shell dissocia...
Source: Chemistry - March 21, 2022 Category: Chemistry Authors: Jintong Liu Bernardino J C órdova Wong Tianrui Liu Hong Yang Lin Yao Ye Jianping Lei Source Type: research

Chemically synthesized, self-assembling small interfering RNA-prohead RNA molecules trigger Dicer-independent gene silencing
Chemistry. 2021 Dec 8. doi: 10.1002/chem.202103995. Online ahead of print.ABSTRACTRNA interference (RNAi) mediated by small interfering RNA (siRNA) duplexes is a powerful therapeutic modality, but the translation of siRNAs from the bench into clinical application has been hampered by inefficient delivery in vivo . An innovative delivery strategy involves fusing siRNAs to a three-way junction (3WJ) motif derived from the phi29 bacteriophage prohead RNA (pRNA). Chimeric siRNA-3WJ molecules are presumed to enter the RNAi pathway via Dicer cleavage. Here, we fused siRNAs to the phi29 3WJ and two phylogenetically related 3WJs. ...
Source: Chemistry - December 8, 2021 Category: Chemistry Authors: Alyssa Hill Dani ël van Leeuwen Verena Schl össer Alok Behera Bogdan Mateescu Jonathan Hall Source Type: research

DNA-Scaffolded Disulfide Redox Network for Programming Drug Delivery Kinetics
Chemistry. 2021 Mar 28. doi: 10.1002/chem.202100149. Online ahead of print.ABSTRACTDynamic covalent materials in response to specific stimuli enable generation of new structures by reversibly forming/breaking chemical bonds, holding a great potential for application in controlled drug release. However, it remains challenging to utilize dynamic covalent chemistry for programming drug delivery kinetics. Here, in situ polymerization-generated DNA-scaffolded disulfide redox network (DdiSRN) is reported by utilizing nucleic acids as scaffold of dynamic disulfide bonds. The constructed DdiSRN in response to redox-stimuli allows ...
Source: Chemistry - March 29, 2021 Category: Chemistry Authors: Wei Ji Xiaodan Li Mingshu Xiao Yueyang Sun Wei Lai Hongbo Zhang Hao Pei Li Li Source Type: research

Photoregulation of Gene Expression with Amantadine-modified Caged siRNAs Through Host/Guest Interaction.
Abstract RNA interference (RNAi) is an essential and powerful tool for targeting and verifying specific gene functions. Conditional control of siRNA activity, especially using light activation, is a potential method to regulate target gene expression and functions. Here, a series of photolabile siRNAs with amantadine modification were rationally designed and developed through host/guest interaction of amantadine and β-cyclodextrin derivatives to enhance the blocking effect of siRNA binding and/or processing. These caged siRNAs with amantadine modification at the 5'end of antisense-strand RNA were efficiently inac...
Source: Chemistry - July 16, 2020 Category: Chemistry Authors: Zhang J, Jing N, Fan X, Tang X Tags: Chemistry Source Type: research

Synthesis and Biological Activity of Short Interfering RNAs Having Several Consecutive Amide Internucleoside Linkages.
In this study, we introduced up to seven consecutive amide linkages at the 3´-end of the guide strand of an siRNA duplex. Modified guide strands having four consecutive amide linkages retained high RNAi activity when paired with a passenger strand having one amide modification between its first and second nucleosides at the 5´-end. Further increase in the number of modifications decreased the RNAi activity; however, siRNAs with six and seven amide linkages still showed useful target silencing. While an siRNA duplex having nine amide linkages retained some silencing activity, the partial reduction of the negative charge d...
Source: Chemistry - November 5, 2019 Category: Chemistry Authors: Kotikam V, Viel JA, Rozners E Tags: Chemistry Source Type: research

MnAl-Layered Double Hydroxide Nanoparticles as a Dual-functional Platform for Magnetic Resonance Imaging and siRNA Delivery.
Abstract Multifunctional nanoparticles for cancer theranosis have been widely explored for effective cancer detection and therapy. In this research, dually functionalised manganese-based layered double hydroxide nanoparticles (Mn-LDHs) have been examined as an effective anticancer drug/gene delivery system and T1-weighted magnetic resonance imaging (MRI) modality for brain cancer theranostics. Such Mn-LDHs have been shown to accommodate dsDNA/siRNAs and efficiently deliver to Neuro-2a cells (N2a). Mn-LDHs have also shown high biocompatibility with low cytotoxicity. Importantly, the cell death-siRNA (CD-siRNA) deli...
Source: Chemistry - August 1, 2017 Category: Chemistry Authors: Zuo H, Chen W, Li B, Xu K, Cooper H, Gu Z, Xu ZP Tags: Chemistry Source Type: research

ROMP- and RAFT-based Guanidinium-containing Polymers as Scaffolds for Protein Mimic Synthesis.
Abstract Cell-penetrating peptides are an important class of molecules with promising applications in bioactive cargo delivery. A diverse series of guanidinium-containing polymeric cell-penetrating peptide mimics (CPPMs) with varying backbone chemistries was synthesized and assessed for delivery of both GFP and fluorescently tagged siRNA. Specifically, we examined CPPMs based on norbornene, methacrylate, and styrene backbones to determine how backbone structure impacted internalization of these two cargoes. Either charge content or degree of polymerization was held constant at 20, with di-guanidinium norbornene mo...
Source: Chemistry - March 28, 2017 Category: Chemistry Authors: Tew GN, Sarpas JM, Backland CM, deRonde BM, Minter LM Tags: Chemistry Source Type: research

Supramolecular Self-Assembly of Histidine-Capped-Dialkoxy-Anthracene: A Visible Light Triggered Platform for facile siRNA Delivery.
Abstract Supramolecular self-assembly of histidine-capped-dialkoxy-anthracene (HDA) results in the formation of light responsive nanostructures.Single-crystal X-ray diffraction analysis of HDA shows two types of hydrogen bonding. The first hydrogen bond is established between the imidazole moieties while the second involves the oxygen atom of one amide group and the hydrogen atom of a second amide group. When protonated in acidic aqueous media, HDA successfully complexes siRNA yielding spherical nanostructures. This biocompatible platform controllably delivers siRNA with high efficacy upon visible light irradiatio...
Source: Chemistry - June 28, 2016 Category: Chemistry Authors: Patil S, Moosa B, Alsaiari S, Alamoudi K, Alshamsan A, Almailk A, Adil K, Eddaoudi M, Khashab N Tags: Chemistry Source Type: research

Synthesis of Site-Specifically Phosphate-Caged siRNAs and Evaluation of Their RNAi Activity and Stability.
Abstract A complete set of new photolabile nucleoside phosphoramidites were synthesized, then site-specifically incorporated into sense or antisense strands of siRNA for phosphate caging. Single caging modification was made along siRNA strands and their photomodulation of gene silencing were examined by using the firefly luciferase reporter gene. Several key phosphate positions were then identified. Furthermore, multiple caging modifications at these key positions led to significantly enhanced photomodulation of gene silencing activity, suggesting a synergistic effect. The caging group on both the terminally phosp...
Source: Chemistry - August 1, 2014 Category: Chemistry Authors: Wu L, Pei F, Zhang J, Wu J, Feng M, Wang Y, Jin H, Zhang L, Tang X Tags: Chemistry Source Type: research