scholarly journals Combining Inulin Multifunctional Polycation and Magnetic Nanoparticles: Redox-Responsive siRNA-Loaded Systems for Magnetofection

Polymers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 889 ◽  
Author(s):  
Carla Sardo ◽  
Emanuela Fabiola Craparo ◽  
Barbara Porsio ◽  
Gaetano Giammona ◽  
Gennara Cavallaro
Keyword(s):  
Magnetic Field ◽  
Nucleic Acid ◽  
Sirna Delivery ◽  
Superparamagnetic Iron Oxide ◽  
Cell Uptake ◽  
Nucleic Acid Delivery ◽  
Crosslinking Process ◽  
Wide Range ◽  
Theranostic Applications

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) are recognized as one of the most promising agents for theranostic applications. Among methods designed for siRNA delivery, magnetofection, that is, nucleic acid cell uptake under the influence of a magnetic field acting on magnetic nucleic acid vectors, is emerging as a unique approach to combining advantages such as strong improvement of the kinetics of the delivery process and the possibility of localizing nucleic acid delivery to an area where the magnetic field is applied. This paper reports on the preparation of siRNA loaded magnetoplexes—named ICD@SS@SPIONs/siRNA—by controlled crosslinking, in the presence of SPIONs, of the polycation INU-C-DETA, synthesized starting from the polysaccharide inulin by grafting diethylenetriamine and cystamine molecules. The obtained ICD@SS@SPIONs/siRNA have suitable chemical-physical characteristics to be employed for iv administration and are also able to release siRNA in a redox-triggered manner thanks to intracellular glutathione (GSH) mediated reduction of disulphide bridges formed during the crosslinking process. Moreover, ICD@SS@SPIONs/siRNA are able to produce magnetic targeting in vitro on breast cancer cells, without appreciable cyto- and hemo-toxic effects, in a wide range of concentrations. Finally, protein binding to nanoparticles revealed that obtained systems are potentially longer circulating and applicable as a smart multifunctional agents for cancer therapy.

scholarly journals Sugar Functionalized Synergistic Dendrimers for Biocompatible Delivery of Nucleic Acid Therapeutics

Polymers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1034 ◽  
Author(s):  
Shuqin Han ◽  
Tsogzolmaa Ganbold ◽  
Qingming Bao ◽  
Takashi Yoshida ◽  
Huricha Baigude
Keyword(s):  
Nucleic Acid ◽  
Sirna Delivery ◽  
Green Fluorescence Protein ◽  
Nucleic Acid Delivery ◽  
Cationic Polymers ◽  
Nucleic Acid Therapeutics ◽  
Fluorescence Protein ◽  
Interfering Rna

Sugars containing cationic polymers are potential carriers for in vitro and in vivo nucleic acid delivery. Monosaccharides such as glucose and galactose have been chemically conjugated to various materials of synergistic poly-lysine dendrimer systems for efficient and biocompatible delivery of short interfering RNA (siRNA). The synergistic dendrimers, which contain lipid conjugated glucose terminalized lysine dendrimers, have significantly lower adverse impact on cells while maintaining efficient cellular entry. Moreover, the synergistic dendrimers complexed to siRNA induced RNA interference (RNAi) in the cells and profoundly knocked down green fluorescence protein (GFP) as well as the endogenously expressing disease related gene Plk1. The new synergic dendrimers may be promising system for biocompatible and efficient siRNA delivery.

scholarly journals Synthetic Histidine-Rich Peptides Inhibit Candida Species and Other Fungi In Vitro: Role of Endocytosis and Treatment Implications

2006 ◽  
Vol 50 (8) ◽  
pp. 2797-2805 ◽  
Author(s):  
Jingsong Zhu ◽  
Paul W. Luther ◽  
Qixin Leng ◽  
A. James Mixson
Keyword(s):  
Nucleic Acid ◽  
Antifungal Activity ◽  
Antifungal Agents ◽  
Fungal Growth ◽  
Nucleic Acid Delivery ◽  
Histatin 5 ◽  
Ph Buffering ◽  
Endosomal Acidification

ABSTRACT A family of histidine-rich peptides, histatins, is secreted by the parotid gland in mammals and exhibits marked inhibitory activity against a number of Candida species. We were particularly interested in the mechanism by which histidine-rich peptides inhibit fungal growth, because our laboratory has synthesized a variety of such peptides for drug and nucleic acid delivery. In contrast to naturally occurring peptides that are linear, peptides made on synthesizers can be varied with respect to their degrees of branching. Using this technology, we explored whether histidine-lysine (HK) polymers of different complexities and degrees of branching affect the growth of several species of Candida. Polymers with higher degrees of branching were progressively more effective against Candida albicans, with the four-branched polymer, H2K4b, most effective. Furthermore, H2K4b accumulated efficiently in C. albicans, which may indicate its ability to transport other antifungal agents intracellularly. Although H2K4b had greater antifungal activity than histatin 5, their mechanisms were similar. Toxicity in C. albicans induced by histatin 5 or branched HK peptides was markedly reduced by 4,4′-diisothiocyanato-stilbene-2,2′-disulfonate, an inhibitor of anion channels. We also determined that bafilomycin A1, an inhibitor of endosomal acidification, significantly decreased the antifungal activity of H2K4b. This suggests that the pH-buffering and subsequent endosomal-disrupting properties of histidine-rich peptides have a role in their antifungal activity. Moreover, the ability of the histidine component of these peptides to disrupt endosomes, which allows their escape from the lysosomal pathway, may explain why these peptides are both effective antifungal agents and nucleic acid delivery carriers.

scholarly journals In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 394 ◽  
Author(s):  
Viktor Maurer ◽  
Selin Altin ◽  
Didem Ag Seleci ◽  
Ajmal Zarinwall ◽  
Bilal Temel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cellular Uptake ◽  
Sirna Delivery ◽  
Superparamagnetic Iron Oxide ◽  
Cost Effective ◽  
Chemotherapeutic Agents ◽  
Therapy Outcome ◽  
Ionic Surfactant ◽  
Combinational Therapy

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

IMMU-53. STING-ING GLIOBLASTOMA WITH SPHERICAL NUCLEIC ACIDS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi104-vi105
Author(s):  
Akanksha Mahajan ◽  
Lisa Hurley ◽  
Serena Tommasini-Ghelfi ◽  
Corey Dussold ◽  
Alexander Stegh ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
High Surface ◽  
Biological Properties ◽  
Innate Immune ◽  
Limiting Factors ◽  
Nucleic Acid Delivery ◽  
Sting Pathway ◽  
Spherical Nucleic Acids

Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that are amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e.,the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently completed early clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway in vitro and in vivo. In a poorly immunogenic and highly aggressive syngeneic mouse glioma model, in which tumours were well-established, only one dose of intranasal treatment with STING-SNAs decelerated tumour growth, improved survival and importantly, was well-tolerated. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites via intranasal route, exploits the binding of dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.

Cationic DOPC-Detergent Conjugates for Safe and Efficient in Vitro and in Vivo Nucleic Acid Delivery

ChemBioChem ◽  
2016 ◽  
Vol 17 (18) ◽  
pp. 1771-1783 ◽  
Author(s):  
Philippe Pierrat ◽  
Anne Casset ◽  
Pascal Didier ◽  
Dimitri Kereselidze ◽  
Marie Lux ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery

scholarly journals Detection and Quantification of the Red Tide Dinoflagellate Karenia brevis by Real-Time Nucleic Acid Sequence-Based Amplification

2004 ◽  
Vol 70 (8) ◽  
pp. 4727-4732 ◽  
Author(s):  
Erica T. Casper ◽  
John H. Paul ◽  
Matthew C. Smith ◽  
Michael Gray
Keyword(s):  
Nucleic Acid ◽  
Real Time ◽  
Wildlife Conservation ◽  
Red Tide ◽  
Diagnostic Testing ◽  
Karenia Brevis ◽  
Nucleic Acid Sequence ◽  
Cell Counts ◽  
Wide Range

ABSTRACT Nucleic acid sequence-based amplification (NASBA) is an isothermal method of RNA amplification that has been previously used in clinical diagnostic testing. A real-time NASBA assay has been developed for the detection of rbcL mRNA from the red tide dinoflagellate Karenia brevis. This assay is sensitive to one K. brevis cell and 1.0 fg of in vitro transcript, with occasional detection of lower concentrations of transcript. The assay did not detect rbcL mRNA from a wide range of nontarget organisms and environmental clones, while 10 strains (all tested) of K. brevis were detected. By the use of standard curves based on time to positivity, concentrations of K. brevis in environmental samples were predicted by NASBA and classified into different levels of blooms per the Florida Fish and Wildlife Conservation Commission (FWC) system. NASBA classification matched FWC classification (based on cell counts) 72% of the time. Those samples that did not match were off by only one class. NASBA is sensitive, rapid, and effective and may be used as an additional or alternative method to detect and quantify K. brevis in the marine environment.

scholarly journals A Direct Comparison of in Vitro and in Vivo Nucleic Acid Delivery Mediated by Hundreds of Nanoparticles Reveals a Weak Correlation

Nano Letters ◽  
2018 ◽  
Vol 18 (3) ◽  
pp. 2148-2157 ◽  
Author(s):  
Kalina Paunovska ◽  
Cory D. Sago ◽  
Christopher M. Monaco ◽  
William H. Hudson ◽  
Marielena Gamboa Castro ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Weak Correlation

A New Generation Nanotherapeutic: pHEMA-Chitosan Nanocomposites in siRNA Delivery

2020 ◽  
Vol 16 ◽  
Author(s):  
Erdal Eroğlu ◽  
Hüseyin Saygın Portakal ◽  
Ayşenur Pamukçu
Keyword(s):  
Ftir Spectroscopy ◽  
Electrostatic Interactions ◽  
Fluorescent Protein ◽  
Sirna Delivery ◽  
Chitosan Nanoparticles ◽  
Average Diameter ◽  
Reticuloendothelial System ◽  
Nucleic Acid Delivery ◽  
Vis Spectroscopy

Background: Despite great hopes for small interfering RNA (siRNA)-based gene therapies, restrictions, including the presence of nucleases, reticuloendothelial system and undesired electrostatic interactions between nucleic acids and the cell membrane, limit the success of these approaches. In the last few decades, non-viral nucleic acid delivery vectors in nano size with high biocompatibility, low toxicity and proton sponge effect have emerged as magic bullets to overcome these drawbacks. Objective: This study aimed to develop poly(2-hydroxyethyl methacrylate) (pHEMA)-chitosan nanoparticles (PCNp), and to transfect green fluorescent protein (GFP)-silencing siRNA (GsiR) in vitro. Method: First, PCNp displaying core-shell structure was synthesized and thereafter GsiR was encapsulated into the core of PCNp. The synthesized PCNp with/without GsiR were characterized using ultraviolet-visible (UV-vis)-spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, thermal decomposition, atomic force microscopy (AFM), scanning electron microscopy (SEM), zeta potential and dynamic light scattering (DLS) measurements. Encapsulation of siRNA into the pHEMA core coated with chitosan shell was demonstrated using fluorescence and FTIR spectroscopy. Results: The surface charge of PCNSs and PCNSs-GsiR were found to be +39.5 and +40.2, respectively. In DLS analysis, an insignificant shift in the Z-average diameter of PCNp was observed from 109 nm to 133 nm using encapsulation of GsiR. In comparison to other studied nanomaterials and a commercial transfection reagent, our findings suggest a promising GFP-silencing effect of 45%. Conclusion: To our knowledge, we have obtained comparable silencing activity with the other studied equivalents despite using the lowest concentration of siRNA in existing literature.

scholarly journals Graphene-Based Nanomaterials for Theranostic Applications

2017 ◽  
Vol 01 (04) ◽  
pp. 1750011 ◽  
Author(s):  
Shounak Roy ◽  
Amit Jaiswal
Keyword(s):  
Graphene Oxide ◽  
High Surface ◽  
Graphene Quantum Dots ◽  
High Surface Area ◽  
Nucleic Acid Delivery ◽  
Efficient Detection ◽  
Reduced Graphene ◽  
Theranostic Applications

Graphene and graphene-based nanomaterials such as graphene oxide (GO), reduced graphene oxide (rGO) and graphene quantum dots (GQDs) have gained a lot of attention from diverse scientific fields for applications in sensing, catalysis, nanoelectronics, material engineering, energy storage and biomedicine due to its unique structural, optical, electrical and mechanical properties. Graphene-based nanomaterials emerge as a novel class of nanomedicine for cancer therapy for several reasons. Firstly, its structural properties like high surface area and aromaticity enables easy loading of hydrophobic drugs. Secondly, presence of oxygen containing functional groups improve its physiological stability and also act as site for biofunctionalization. Thirdly, its optical absorption in the NIR region enable them to act as photoagents for photothermal and photodynamic therapies of cancer, both in vitro and in vivo. Finally, its intrinsic fluorescence property helps in bioimaging of cancer cells. Overall, graphene-based nanomaterials can act as agents for developing multifunctional theranostic platforms for carrying out more efficient detection and treatment of cancers. This review provides a detailed summary of the different applications of graphene-based nanomaterials in drug delivery, nucleic acid delivery, phototherapy, bioimaging and theranostics.

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