scholarly journals Self-assembling asymmetric peptide-dendrimer micelles – a platform for effective and versatile in vitro nucleic acid delivery

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Ganesh R. Kokil ◽  
Rakesh N. Veedu ◽  
Bao Tri Le ◽  
Grant A. Ramm ◽  
Harendra S. Parekh
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Self Assembling ◽  
Peptide Dendrimer

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.

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 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

Sterically stabilized self-assembling reversibly cross-linked polyelectrolyte complexes with nucleic acids for environmental and medical applications

2009 ◽  
Vol 37 (4) ◽  
pp. 713-716 ◽  
Author(s):  
Martin C. Garnett ◽  
Paolo Ferruti ◽  
Elisabetta Ranucci ◽  
Marco A. Suardi ◽  
Mieke Heyde ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Field Trials ◽  
Cross Linking ◽  
Medical Applications ◽  
Nucleic Acid Delivery ◽  
Poly Ethylene Glycol ◽  
Polyelectrolyte Complexes ◽  
Self Assembling ◽  
Poly Ethylene ◽  
Future Work

One of the principal problems facing nucleic acid delivery systems using polyplexes is the instability of the complexes in the presence of proteins and high salt concentrations. We have used a cross-linking polymer to overcome this problem. Pendant thiol moieties have been incorporated into a PAA (polyamidoamine) homopolymer and a PEG [poly(ethylene glycol)]–PAA–PEG copolymer reported previously as a self-assembling system. When mixed with DNA, small monodisperse sterically stabilized particles are formed in quantitative yields. Optimization of the formulation resulted in nanoparticles which are stable in seawater. This cross-linked formulation has been successfully tested in both freshwater and estuarine field trials as a water tracer. Future work will develop these particles as a groundwater tracer and also for therapeutic applications of nucleic acid delivery.

Components Simulation of Viral Envelope via Amino Acid Modified Chitosans for Efficient Nucleic Acid Delivery: In Vitro and In Vivo Study

2012 ◽  
Vol 23 (21) ◽  
pp. 2691-2699 ◽  
Author(s):  
Jing Chang ◽  
Xianghui Xu ◽  
Haiping Li ◽  
Yeting Jian ◽  
Gang Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nucleic Acid ◽  
Viral Envelope ◽  
In Vivo Study ◽  
Nucleic Acid Delivery

scholarly journals Tunable Composition of Dynamic Non-Viral Vectors over the DNA Polyplex Formation and Nucleic Acid Transfection

Polymers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1313 ◽  
Author(s):  
Lilia Clima ◽  
Bogdan Florin Craciun ◽  
Gabriela Gavril ◽  
Mariana Pinteala
Keyword(s):  
Molecular Weight ◽  
Nucleic Acid ◽  
Viral Vectors ◽  
Viral Vector ◽  
Transfection Efficiency ◽  
Binding Capacity ◽  
Nucleic Acid Delivery ◽  
Force Microscopy ◽  
Transmission Electron

Polyethylene glycol (PEG) functionalization of non-viral vectors represents a powerful tool through the formation of an overall surface charge shielding ability, which is fundamental for efficient nucleic acid delivery systems. The degree of non-viral vector PEGylation and the molecular weight of utilized PEG is crucial since the excessive use of PEG units may lead to a considerable reduction of the DNA-binding capacity and, subsequently, in a reduction of in vitro transfection efficiency. Herein, we report a detailed study on a series of dynamic combinatorial frameworks (DCFs) containing PEGylated squalene, poly-(ethyleneglycol)-bis(3-aminopropyl) of different lengths, and branched low molecular weight polyethylenimine components, reversibly connected in hyperbranched structures, as efficient dynamic non-viral vectors. The obtained frameworks were capable of forming distinct supramolecular amphiphilic architectures, shown by transmission electron microscopy (TEM) and dynamic light scattering (DLS), with sizes and stability depending on the length of PEG units. The interaction of PEGylated DCFs with nucleic acids was investigated by agarose gel retardation assay and atomic force microscopy (AFM), while their transfection efficiency (using pCS2+MT-Luc DNA as a reporter gene) and cytotoxicity were evaluated in HeLa cells. In addition, the data on the influence of the poly-(ethyleneglycol)-bis(3-aminopropyl) length in composition of designed frameworks over transfection efficiency and tolerance in human cells were analyzed and compared.

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 1,28-Di[(cholest-5-en-3β-yl)disulfanyl]-4,25-dioxo-3,8,12,17,21,26-hexaazaoctacosane tetrahydrochloride

2018 ◽  
Author(s):  
Pavel A. Puchkov ◽  
Elena V. Shmendel ◽  
Valeria D. Andreeva ◽  
Nina G. Morozova ◽  
Marina A. Zenkova ◽  
...  
Keyword(s):  
Thin Film ◽  
Gene Therapy ◽  
Nucleic Acid ◽  
Transfection Efficiency ◽  
Cationic Liposomes ◽  
Hek293 Cells ◽  
Nucleic Acid Delivery ◽  
Promising Candidate ◽  
Effective Delivery

The absence of highly effective delivery systems is a major challenge for gene therapy. Our work was aimed at the development of novel cationic liposomes possessing high transfection efficiency. For this purpose, a novel disulfide polycationic amphiphile 2S4 was synthesized. Cationic liposomes based on 2S4 and a helper lipid DOPE were formed by the thin film hydration method and exhibited effective pDNA delivery into the HEK293 cells, with a maximal transfection activity superior to that of the commercial agent Lipofectamine® 2000. Our results suggest that the polycationic amphiphile 2S4 is a promising candidate for in vitro nucleic acid delivery.

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